
Class 

Book 

GqipglitW. 



COFSRIGHT DEPOSm 



THE INTERNAL SECRETIONS 
IN PRACTICAL MEDICINE 



THE INTERNAL SECRETIONS 
IN PRACTICAL MEDICINE 



V 



BY 



HENRY R.^ HARROWER, M. D. 

Fellow of the Royal Society of Medicine (London) 

Sometime Professor of Clinical Diagnosis, 

Loyola University, Chicago; Member 

American Medical Editors 

Association; etc. 



CHICAGO 

CHICAGO MEDICAL BOOK CO. 

1917 



.H3 



AUG 20 1917 



©CI,A470696 



^ 



Wthitni^^ lit 

^. ^., -f^. ?, ^t. ^. 

to whom, more than to any other man, practicing 
physicians in the United States are indebted for 
painstaking and persistent efforts to make clear 
the importance of the glands of internal secre- 
tion through his book, "The Internal Secretions 
and the Principles of Medicine," and his numer- 
ous other writings ; and for directing attention 
to facts concerning the functions of these organs 
which, though long discounted by some, are now 
increasingly being accepted by the profession. 



Copyright 1917 by 
HENRY R. HARROWER, M. !>. 




Printed in the United States of America 



TABLE OF CONTENTS 



I Introduction : Broadening the Scope of the 

Practice of Medicine 1 

II The Internal Secretions with Special Reference 

to the Treatment of Chronic Disease 6 

III The Relation of the Endocrine Glands to Func- 

tional Disorders 16 

IV The Inconscpicuous, Every-day Forms of Thy- 

roid Insufficiency 30 

V Pluriglandular Insufficiency: its Incidence and 

Treatment -- -. 43 

VI Shell Shock (Neurasthenia) and the Internal 

Secretions, with Suggestions as to Treat- 
ment - - - 62 

VII The Adrenal Glands and their Significance in 

General Practice — 76 

VIII The Asthenias : Myasthenia, Neurasthenia, 

Chemasthenia and Psychasthenia — Endocrin- 
asthenia 91 

IX The Relation of the Internal Secretions to 
y< Neruasthenia in Women 100 

X Sex Disabilities Considered as Endocrine Dys- 

crasias 114 

XI The Relation of the Internal Secretions to 

Rheumatism and the Rheumatic Diathesis.... 123 

XII The Relation of the Thyroid Gland to Epilepsy 136 

XIII The Defective Child from the Standpoint of the 

Internal Secretions 148 

XIV Organotherapy in Chronic Disease with Spe- 

cial Reference to its Possibilities in Cancer.... 163 

XV Some Remarks on the Treatment of Hyper- 

thyroidism 185 



viii THE INTERNAL SECRETIONS 

XVI The Mamma as an Internal Secretory Organ : 

Mammary Therapeutics 196 

XVII Connecting Links between Endocrinology and 

Oto-Rhinology 212 

XVIII The Treatment of Rickets 222 

XIX The Oral Administration of Adrenalin 229 

XX The Adjunct Treatment of Tuberculosis with 

Certain Organic Extracts 237 



PREFACE 

A NUMBER of phAT^sicians, especially those who 
have read or heard one or more of my papers on 
subjects related to the glands of internal secretion, 
have expressed a desire to have some of them avail- 
able in more permanent form. Hence this collec- 
tion of articles in book form. 

Unlike my earlier book, "Practical Hormone 
Therapy : a Manual of Organotherapy for Practi- 
tioners" (which is referred to occasionally in the 
following pages), the units comprising this col- 
lection were not written originally with the in- 
teniton of fitting them together as harmoni- 
ous and consecutive whole. As a result of this 
there is a certain amount of redundancy which it 
has seemed best to leave unmodified. As these re- 
iterations have been reread for publication in this 
present form, the fact has been emphasized that no 
harm can come from reading some essential more 
than once, especially when the repetition lends 
weight to some particular contention in one paper 
and to a different one in another. 

Several additional paragraphs have been added 
to a number of the articles as originally published 
in the medical press, with the idea of making them 
more comprehensive and as up-to-date as possible. 
As a matter of fact quite a number of experiences 
have been reported in current literature which amp- 
lify my position in a previously published report. 



X THE INTERNAL SECRETIONS 

and their inclusion here adds emphasis to what may 
have been said. 

No attempt has been made to cover the entire 
subject. It is far too vast. In fact it would take 
a small library to include all the information now 
at our disposal regarding the glands of internal se- 
cretion and their hormones. However some time 
has been spent in preparing a fairly complete index 
so as to facilitate the study of various phases of the 
subjects covered which may be of immediate inter- 
est to the reader and 3^et be discussed in more than 
one chapter in the book. 

For a more complete consideration of the thera- 
peutic side of this subject the reader is referred to 
my book mentioned above; and also to a quarterly 
journal entitled "ENDOCRINOLOGY" which is 
a periodical reviev/ of the current literature on all 
phases of this subject. This journal is published 
by the Association for the Study of the Internal 
Secretions, which I assisted in starting in 1916. 
Further information regarding the activities of this 
Association will be sent to any interested physician 
on request. 

My thanks are due to a number of colleagues for 
the encouragement given me to have these papers 
collected in this form, as well as to the publishers 
of various medical journals in the United States 
and Great Britain in which some of the chapters 
already have appeared, for the privilege of reprint- 
ing them in this form. 



IN PRACTICAL MEDICINE ix 

I realize that some of my statements are open to 
criticism, and I will welcome any constructive criti- 
cal remarks or queries. I do not profess to be more 
than an ardent student of what is to me a very fas- 
cinating subject. 

I need not apologize for my interest in this sub- 
ject, nor for the enthusiasm it has engendered. I 
only hope that some hint in this book may serve to 
make a real difference to some reader's considera- 
tion of a difficult case; and that as a result of read- 
ing it some tangible advantage may accrue to both 
patient and physician. 

HENRY R. HARROWER. 
Glendale, California. 
July, 1917. 



THE INTERNAL SECRETIONS 
IN PRACTICAL MEDICINE 



INTRODUCTION: 

BROADENINCx THE SCOPE OF THE 
PRACTICE OF MEDICINE 

AS our knowledge of physiology becomes more 
intimxate and our application of some of the ideas 
set forth by the experimentalists are put into prac- 
tice, we find the scope of medical practice broad- 
ening in a remarkable manner. Revolution follows 
revolution until the standardized procedures of to- 
day differ as radically from those of, say, 25 years 
ago as do the present conceptions of the physio- 
logic relations of the various parts of the body com- 
pared with those held at that time. 

Undoubtedly the most radical as well as impor- 
tant advance in medicine is our better knowledge 
of the endocrine system — that interlocking, though 
widely separated, collection of glands of internal 
secretion wdiich we now know is in supreme con- 
trol of growth, both physical and mental; metabo- 
lism; the sympathetic nervous system, with its reg- 
ulation of vascular tone and blood pressure; as well 

(1) 



2 THE INTERNAL SECRETIONS 

as the indefinite and complex factors gathered to- 
gether into the one well-known term "constitu- 
tion." The hormones produced by these wonder- 
ful glands are secreted into the blood and serve to 
correlate function and harmonize many of the 
widely differing functions of the body. Their 
chemical messages are of such a nature that to ig- 
nore them and their subtle influence is to miss a 
very large and important part of the information 
which may be at the disposal of any observant phy- 
sician. 

Just as the discovery of the hormones and the un- 
ravelling of the intricate skein of their relationships 
has revolutionized physiology, so the knowledge 
we have been able to deduce from these facts is 
revolutionizing therapeutics, for it is now generally 
recognized that organotherapy is making possible 
the successful treatment of many chronic and com- 
plicated disorders. 

The study of these endocrine glands will well re- 
pay the interested reader of the hundred and one 
articles and abstracts now appearing in current 
medical literature; and as he applies the obvious 
treatment in a given case, he will be both surprised 
and pleased at the results which so often follow 
the application of this altogether scientific and rea- 
sonable branch of therapy. 

It is not necessary within the limits of this brief 
introduction to do more than direct attention to 



IN PRACTICAL MEDICINE 3 

the great possibilities of this phase of medicine; 
and to outline the essential facts upon which the 
science of practical hormone therapy has been 
built. 

By far the greatest principle is that of "homo- 
stimulation," which is included in what has come 
to be known as Hallion's law, which is as follows: 
"Extracts of an organ exert on the same organ an 
exciting influence which lasts for a longer or 
shorter time. When the organ is insufficient it is 
conceivable that this influence augments its action 
and, when it is injured, that it favors its restora- 
tion." This has been demonstrated experimentally 
and clinically so many times, that it is almost axi- 
omatic, though it is not infallible, and may still be 
criticized occasionally by some. Granting what 
Hallion has said, functional insufficiencies of many 
of these organs may be expected to be favorably 
influenced by giving suitable doses of the corre- 
sponding gland secured from animals. 

Closely allied to this is another slightly different 
phase of organotherapy. Frequently it is not suf- 
ficient to attempt to stimulate a lagging gland. One 
must replace, in part at least, the missing substance 
that it should have been furnishing to the body. 
This is what is known as "substitutive organother- 
apy." In conditions like cretinism or infantilism 
where the thyroid or gonads are absent, one can 
measurably restore the activity that is reduced or 
absent because of the lack of the hormone stimuli 



4 THE INTERNAL SECRETIONS 

from the glands in question. In severe functional 
conditions we expect to benefit from organother- 
apy in at least two ways — by substituting for the 
missing hormones and, also, by causing what is 
known as homostimulation, the principle so well 
described in Hallion's law just quoted. 

Again the chemical substances produced in the 
normal physiologic action of certain of the duct- 
less glands have a definite pharmacological action 
and its application in medicine is the so-called 
"specific organotherapy," for the influence of the 
drug — these extracts must be considered purely as 
drugs — favors some desirable action as, for in- 
stance, the stimulation of the uterus with the pos- 
terior pituitary principle during a delayed labor. 
In such a case there is no evidence whatever to 
prove that this hormone principle is absent or even 
that the pituitary is not working normally. We 
simply make use of the specific action of this sub- 
stance. 

Finally in our clinical and laboratory experi- 
menal work we have found that the administration 
of certain "extracts" (as they are usually but, in 
some instances, erroneously, called) cause certain 
physiologic reactions and we make use of these 
facts by applying what is, strictly speaking, "em- 
pirical organotherapy." 

No matter in what conditions organotherapy 
may be used, irrespective of its "scientific" or its 
"empirical" basis, it is a valuable addition to our 



IN PRACTICAL MEDICINE 5 

medical armamentarium, for where its application 
is physiologically proper one may expect it to give 
results and therefore be rational, while in the not 
infrequent cases where there may be a question 
about the the exact raison d'etre of a certain or- 
ganotherapeutic remedy, it is rational because it is 
resultful. "We care not how the results come, pro- 
vided they come, and come quickly." 

Organotherapy, however, is only a small part of 
endocrinology; a part of it which has not yet recov- 
ered from the rank empiricism and quackery of a 
few decades ago. The study of the relations of the 
glands of internal secretion whether followed by 
the application of organotherapeutic procedures or 
not, is of great importance; and as various phases 
are considered from certain practical points of 
view, it will be clear that the remark of one writer 
— ''in these days the internal secretions are being- 
studied as never before, and most assuredly are 
coming into their own" — is perfectly true; and that 
there is plenty of excuse for the widespread interest 
now being accorded to this growing branch of 
medicine. 

The more time and attention that is given to the 
practical study of endocrinology, the broader will 
be the scope of the practice of medicine and the 
greater the professional prestige and profit of the 
aggressive physician who measures and applies the 
advances in medicine by the only reasonable stand- 
ard — the standard of ''tests-and-results." 



II 

THE INTERNAL SECRETIONS WITH SPE- 
CIAL REFERENCE TO THE TREAT- 
MENT OF CHRONIC DISEASE 

THE rapidly increasing fund of information 
which students of endocrinology are making avail- 
able for interested members of the profession, is 
modifying many of our conceptions of internal 
medicine as well as changing some of our ideas re- 
garding treatment. 

As we bring these facts to bear upon numerous 
and widely differing phases of medical practice, it 
soon becomes clear that a great fundamental prin- 
ciple is involved, which neither the skepticism of 
the ignorant nor the passage of time can change. 
The hormones, or active principles elaborated by 
the glands of internal secretion, exert a decided in- 
fluence upon those factors concerned in the causa- 
tion as well as the cure of the majority of chronic 
diseases. Hence, hormone therapy, or the use of 
animal extracts in therapeutics, contains potentiali- 
ties worthy of practical consideration by those who 
treat the numerous persistent and intractable ills 
which the flesh seems to be inheriting in increasing- 
degree. 



An address read before the Southern California Medical So- 
ciety at Los Angeles, California, December 2nd, 1915. 

(6) 



IN PRACTICAL MEDICINE 7 

The subject is still in its formative stage, and 
occasionally one finds those who look at it askance, 
despite the innumerable encouragements which we 
are constantly meeting from day to day. I just 
happened to pick up the current issue of the Ameri- 
can Journal of Obstetrics (Nov., 1915, p. 885), and 
read an interesting discussion on the value of cor- 
pus luteum therapy. One of the participants, Dr. 
A. T. Jones, of Providence, made a statement which 
I would like to repeat : 'With reference to organo- 
therapy, I think the profession is divided into two 
classes. As a rule one class loses its head over or- 
ganotherapy and believes everything can be cured 
by organic extracts" — and, by the way, I have been 
put into this class because my recent book, "Prac- 
tical Hormone Therapy," merely for the sake of 
comprehensiveness, takes up some forms of organo- 
therapy with which I have no experience, because 
I have little faith in them — "while the other class 
is that group who would not give organic extracts 
even if they knew they were going to get a good 
result. They will not take it up; they never have 
tried it. I believe these extracts are of value, and 
particularly the corpus luteum extract." 

The writer fully agrees with Dr. Jones, and while 
one meets more men who should be in the second 
as compared with the first class, I am finding an in- 
creasing number of progressive physicians who are 
open to conviction and who, realizing the vast pos- 
sibiHties of this study, are exploring its depths and 



8 THE INTERNAL SECRETIONS 

finding many most pleasing experiences there. In 
the same discussion just referred to, Leighton, in 
concluding, said: ''This therapy has its limitations. 
It is not a cure-all. There is one trouble, and that 
is we do not use it enough!" And this applies in 
other equally practical phases of the subject to 
which brief allusion shortly will be made. 

With very few exceptions, all chronic diseases 
have associated with them, and are aggravated by, 
a disturbance in one or more of the internal secre- 
tory organs. If this position is correct, we have 
another angle from which to consider those of our 
patients who are chronic sufferers. Many articles 
and editorials in our own and foreign medical lit- 
erature (and, parenthetically, it must be admitted 
that abroad the}^ do more work in this line, hence 
more information is to be found in the French, 
Italian and English literature) direct attention to 
the new avenues of therapeutic endeavor that are 
being opened up. And they are being well trav- 
eled. Organotherapy is being studied as never be- 
fore, and those who are attracted by its fascina- 
tions, are learning that the results sometimes at- 
tained are not simply good, but wonderful. 

You all have personal knowledge of the diverse 
therapeutic possibilities of the principle from the 
'infundibulum of the pituitary body first suggested 
as a remedy by Blair Bell, of Liverpool, as late as 
1909. You know of its startling effects upon the 
uterus in labor and of its value as a postpartum 



IN PRACTICAL MEDICINE 9 

remedy, its influence in such remote conditions as 
intestinal paresis, anuria and agalactia; and finally 
of its definite value as a heart tonic. In fact in a 
personal letter from the late Sir Lauder Brunton, 
he remarked that pituitrin was a more efficient 
heart stimulant than either digitalis or strychnia, 
and it is none too often used for this purpose either. 
Now I haAX not enumerated all the advantages of 
this single remedy and there are other organo- 
therapeutic preparations almost as wonderful. 

None the less to some ''it is still too early to pass 
judgment," and as another put it, ''we are still 
groping in the very dimly lighted recesses of this 
new study." However, it is encouraging to recall 
that a single experience is worth ten times as much 
as an argument; and the tests-and-results method 
is the only way to convince one's self that what 
may be said here to-night is not just the dream of 
a visionary crank. 

Obviously we cannot more than refer to the mere 
fundamentals involved in the relation of the in- 
ternal secretions to the incidence and control of 
chronic disease. We can, however, refresh our 
minds on a few of the better known matters and, 
perhaps, hint briefly of some of the other possibili- 
ties of this rapidly advancing and increasingly in- 
teresting siibject. 

Probably more has been written about the thy- 
roid than about any of the other glands of internal 
secretion. It has been most carefully studied for 



10 THE INTERNAL SECRETIONS 

many years and its pathology and physiology are 
only just beginning to be fairly well understood; 
in fact, though this is probably the best known of 
the endocrine glands, we are not yet able to isolate 
its active principles,* and we have still much to 
learn of the intricacies of its physiologic relations. 
The epoch-making work of George Murray, now 
of Manchester, in the original application of thy- 
roid therapy in the major thyroid disorders myxe- 
dema and cretinism, seems to have directed atten- 
tion far beyond the much more common minor thy- 
roid insufficiencies, and evidence of this is found 
in the last U. S. P., for in it the dosage of desiccated 
thyroids is given as 5 grains, an altogether pre- 
posterous dose in the majority of the conditions in 
which thyroid is now used. Instead of this pharma- 
copoeial dose, which, by the way, may be quite rea- 
sonable in certain cases of athyroidia and severe 
thyroid disorders, we now rarely use more than one 
grain and frequently a quarter or half a grain three 
times a day is quite sufficient to bring about very 
satisfactory results. 

The thyroid gland is functionally disturbed, 
slightly in some cases, more in others, in many 
every-day conditions, many of which are chronic 
in their manifestations. Those disorders which are 
dependent upon perversions of the metabolism — 



♦Since this was written a communication from the Mayo 
Clinic by E. C. Kendall announces the discovery there of what ap- 
pears to be the active principle of the thyroid gland. 



IN PRACTICAL MEDICINE II 

rheumatism, gout and perhaps, in some degree, dia- 
betes — usually have a thyroid element of greater or 
less importance. Following the original work of 
my very good friend. Dr. Eugene Hertoghe, of 
Antwerp, Leopold Levi and his associate. Baron 
Henri de Rothschild, of Paris, have made a most 
minute study of the part that the thyroid plays in 
almost every disorder. Every patient who comes 
to their hospital virtually is studied as a thyroid 
case, and in their recent book, "La Petite Insufifi- 
sance Thyroidienne et son Traitement," it is re- 
markable to note how large a variety of conditions 
have a distinct thyroid aspect and, more practical 
yet, are either directly benefited by the administra- 
tion of thyroid or the regular treatment is made 
more effective by the addition of one or two centi- 
grammes of thyroid per day. More than forty dis- 
orders are in this category from neurasthenia to 
psoriasis. Yet, like most enthusiasts, they have 
been laughed at, and sneered at, too, for fifteen 
years or more. Still Levi and de Rothschild have 
mastered the technique of thyroid medication and 
use it with much advantage in many conditions, 
both distinctly thyroid in origin and in which no 
obvious thyroid disturbance can be found. In this 
country we have still a few things to learn in this 
particular corner of this field. 

Closely related to thyroid hypofunction is the 
condition known as pluriglandular insufficiency, an 
extremely common symptom complex which is 



12 THE INTERNAL SECRETIONS 

more than occasionally overlooked. The statement 
recently has been made that disorders of the hor- 
mone-bearing organs always affect more than one 
gland, since the intimacy of these organs renders it 
impossible for one gland to be disturbed without an 
associated disturbance in one or more of the others 
related to it. There are two principal forms of 
pluriglandular insufficiency, the organic and the 
functional. The former commonly asserts itself in 
certain developmental disorders and in syphilis. 
Right here is a phase of syphilology which deserves 
cloesr attention. In a paper which I prepared for 
a special issue of The Practitioner (London), on 
Pluriglandular Insufficiency,* a number of reports 
were collated showing the relation of syphilis to 
ductless glandular syndromes. In such cases the 
information has usually been elicited at the autopsy 
table, though several cases of obvious endocrine 
disorder were traced to syphilis and treated with 
comparative satisfaction. The chief deduction that 
may be made from this is that syphilis as a general- 
ized disease, may and does affect the hormone 
producing system and its treatment may be ex- 
tended by adding to the usual arsenic or mercury 
treatment, suitable organotherapeutic extracts to 
stimulate the various semi-active ductless glands 
and thus cause a general betterment not otherwise 
attained. 

In this connection an abstract in the Journal of 



*Chapter V of this book. 



IN PRACTICAL MEDICINE 13 

the American Medical Association (October 2, 
1915, p. 1223), is instructive. ''A striking case is 
reported by Korczynski in which inherited syphiHs 
seems to have impaired the functioning of the thy- 
roid, hypophysis, ovaries and blood-producing or- 
gans. The child was mentally backward. Thyroid 
treatment and treatment for syphilis were given to- 
gether, and a pronounced change for the better was 
soon apparent and has continued to progress. . . ." 
The functional forms of pluriglandular insuffi- 
ciency are not associated with the obvious mani- 
festations that the more marked organic conditions 
usually show. The reduced production of the 
''chemical messengers" is none the less present, for 
when an individual is run-down, for instance, when 
the elimination is not as it should be, when the 
muscles are easily fatigued, the nerves easily ex- 
cited and there are present the other usual manifes- 
tations of neurasthenia and debility, one can hardly 
believe that 4:he glands of internal secretion alone 
are working normally. In such cases pluriglandu- 
lar therapy is an exceptionally useful treatment, 
alone or combined with other treatment which the 
exigencies of the case may indicate. It may be 
w^ell, incidentally, to remark that in ovarian dis- 
orders where luteal therapy is indicated and likely 
to be effective, the addition of some of the extracts 
of glands known to be intimately related to the 
gonads, the thyroid and the pituitary, will more 



14 THE INTERNAL SECRETIONS 

than likely make the response to treatment more 
decided and resultful. 

The control of the sympathetic nervous system 
by the chromaffin hormone produced in the medul- 
lary portion of the adrenal glands, makes these or- 
gans of supreme importance in numerous condi- 
tions. Take that most common of all clinical mani- 
festations, pain, and recall that it has been shown 
by competent investigators to be a decided stimu- 
lant to the adrenals and thus 'Vears them out." 
This is a partial explanation, at least, of the 
clinical value of preparations of this character in 
many disorders including cholera (with its extreme 
pain and collapse), shock (with its associated acute 
adrenal insufficiency first intelligently discussed by 
Sajous, of Philadelphia about 13 years ago), post- 
febrile collapse or asthenia (conditions definitely 
traced to hypoadrenia and just as definitely bene- 
fited by the obvious therapeutic procedure — the ad- 
ministration of adrenaHn or similar products), and 
other important disorders. 

Crile's valuable studies which have given us 
anoci-association and the power to reduce or en- 
tirely eliminate post-anesthetic shock by removing 
the stimuH which unduly overwork the kinetic sys- 
tem, are based in a large measure upon the physio- 
logical chemistry of the adrenal medulla, and while 
his most profitable work has been of a prophylactic 
nature — to prevent the unpleasant results at one 
time not infrequently following operations, the 



IN PRACTICAL MEDICINE 15 

same principle applies in therapeutics, for when the 
adrenals have been depleted and the body is suffer- 
ing from the lack of the normal amount of adrenin, 
with low blood pressure, asthenia and collapse, the 
natural thing to do is to secure the missing sub- 
stance from animals and give it as quickly and di- 
rectly as possible, just as we have learned to do the 
same thing with thyroids from sheep or corpora 
lutea from sows. 

Now you realize, of course, that this subject 
which was chosen on the spur of the moment as 
the result of a telegraphic request by your Secre- 
tary to my friend. Col. McCullough, of the Sur- 
geon-General's Library in Washington, has been 
considered only in its broadest general aspects. It 
is as broad as the influence of the hormones upon 
physiology, and the limits of its practical useful- 
ness have not yet been reached, although we have 
already learned many, many things. 

There is much more, and the more we study and 
apply these principles in our work, and especially 
that part of it which concerns the treatment of 
chronic disorders, the more we appreciate the en- 
thusiasm of many who are daily delving into these 
secrets and are finding in them so much that is 
available in the every-day routine of medicine. 



Ill 

THE RELATION OF THE ENDOCRINE 
GLANDS TO FUNCTIONAL DISORDERS 

WHILE the study of the glands of internal se- 
cretion has received a great impetus in the past few 
years, and the science underlying the diagnosis and 
treatment of endocrine disorders certainly has ad- 
vanced greatly in this period, there is still a v^ell- 
defined tendency to consider ductless glandular dis- 
ease per se rather than the functional pathology 
resulting from modifications in the chemical activ- 
ities of these glands. 

Disorders of function obviously are of far greater 
clinical importance than organic disease not merely 
because of their much greater frequency, but be- 
cause the former are merely more or less slight 
aberrations from the average, whereas the latter 
involve structural changes which in many cases are 
only partially amenable to the very best of treat- 
ment. 

The discovery of cretinism, myxedema, the Ad- 
dison, Froehlich or Graves syndromes is compara- 
tively easy, for each of these conditions is a dis- 
ease with a more or less definite pathology and 
symptomatology. But the insidiousness of func- 



Read in a Symposium on Functional Pathology before the 
Sections on Medicine and Neurology, California State Medical So- 
ciety at Coronado, April, 1917. 

(16) 



IN PRACTICAL MEDICINE 17 

tional pathology of the glands of internal secretion 
and the frequency with which disturbances of their 
functions play a part in many acute as well as 
chronic conditions of every day occurrence, makes 
their study of greater clinical importance than the 
more definite and easier demonstrated ductless 
glandular diseases of which a few have just been 
enumerated. 

With our added knowledge of the physiology of 
the endocrine glands and its importance, we are 
enabled to study many a functional condition from 
a viewpoint which is considerably different from 
that of past years, and this may enable us so to 
modify our treatment that many of the hitherto 
intractable disorders may now respond to our 
efforts. 

In an editorial in the New York Medical Jour- 
nal (1) published a few months ago, the importance 
of functional medicine was emphasized and it was 
remarked that in order that the advances in the 
pathological sciences might be fully appreciated 
and be of the greatest usefulness ''there is need 
for a better understanding of fundamental physio- 
logical principles and a much wider appreciation 
of functional possibilities. To this must be added 
the ability to correlate new findings and to detect 
departures from the normal in their early stages. It 
is only from such studies as these that we may hope 
to acquire that breadth and keenness of vision so 
essential to-day to offset the narrowness and con- 



18 THE INTERNAL SECRETIONS 

centration of specialism/' As a result of this, in 
the words of the same editorial writer just referred 
to, "our diagnoses will become more fundamental 
and our therapeutics more vital." 

I have seen many a case with the diagnosis of 
rheumatism or tuberculosis or neurasthenia or in- 
digestion in which the ductless glandular element 
was not even thought of. Why should a physician 
study the thyroid activity of a patient with tubercu- 
losis, or connect the adrenals with neurosis? As a 
matter of fact, it is impossible for a severe infection 
like rheumatism or a protracted disease like tuber- 
culosis not to make a very decided mark upon one 
or more of the glands of internal secretion, and 
since these glands respond so easily to the influence 
of infections, toxemias or even psychological 
states, it takes but a short time to involve them. 

It can be taken for granted that questions con- 
cerning therapeutics always must be matters of 
opinion in which unanimity is unlikely; but ques- 
tions of pathologic physiology are now being ascer- 
tained with precision and the subject is being put 
upon such a basis that dissent is not so probable. 
At least the relations of certain functions of the 
body are now sufficiently understood so that we 
can refer to them with confidence and it is to some 
of these that I wish to direct your attention to-day. 

Every function of the body is in some way di- 
rectly or remotely connected with the work of the 
endocrine glands, hence disorder in them invari- 



IN PRACTICAL MEDICINE 19 

ably, let me emphasize this word, spells disorder iti 
other functions. So really the functional pathology 
of the endocrine glands is reflected in almost every 
phase of the practice of medicine, for growth, 
metabolism, oxidation, resistance to infection and 
the more indefinable but none the less important 
fundamentals, constitution and temperament, are 
now considered to be dependent upon ductless 
glandular action. 

Furthermore the clinical leading of information 
of this character prompts us to use measures in the 
place of or in conjunction with those to which we 
have become accustomed, and such modifications 
of the treatment are a decided advantage towards 
greater success. In other words, when we are con- 
sidering a given disease we will find out more of 
value and be able to render a more satisfactory 
service if the functional pathology of the endocrine 
organs is also considered — if we consider the pa- 
tient as a whole rather than his disease as a unit. 
As yet, however, this is not the rule, for there still 
seems to be a tendency to study diseases instead 
of patients, and to treat certain text-book symp- 
toms with whatever measures may be uppermost 
in the physician's mind. 

Our knowledge of clinical endocrinology might 
be considerably better, at least in so far as discern- 
ing the earliest beginnings of these subtle influ- 
ences is concerned. It is not in the discovery of 
well-differentiated disorder, but in the appreciation 



20 THE INTERNAL SECRETIONS 

of the ordinary chemical changes of the beginnings 
of disease — the early steps in functional pathologi- 
cal change — that one attains the best results and 
the greatest personal satisfaction. 

In an editorial note on cancer, Clinical Medi- 
cine (2) remarks: "We still are in constant pro- 
test against the neglect of the study of physiology 
now prevalent in the entire profession. Over and 
over again v^e have urged upon the profession the 
importance of so studying the physiology of the 
human body that the very first departure from nor- 
mal activity of any of the functions shall be de- 
tected and the cause of such departure removed. . . . 
To the chemistry of the blood, we must look for the 
essential cause of cancer." 

Physiology is too complex for internal medicine, 
much less the other branches of medicine, to be re- 
duced to one single phase of study. The broader 
our conceptions of the physiologic functions of the 
body, the more intimate is our knowledge of the 
cellular interrelationships of the various integral 
parts of the organism; and hence the greater is our 
appreciation of the importance of more or less in- 
significant modifications of these relationships — or 
''functional pathology" as it is called. 

Since we have begun comparatively recently to 
realize the comprehensiveness of the so-called 
''hormone balance," we have also naturally had our 
eyes opened to the importance of aberrations in 
one or more of the elements which go to maintain 



IN PRACTICAL MEDICINE 21 

this balance; and disordered function, be it ever so 
slight, now frequently directs attention to an in- 
significant thyroid, pituitary or other endocrine 
complex which until very recently invariably was 
overlooked. 

It may not be possible to substantiate this posi- 
tion in the mind of every skeptic in the brief time 
allotted; but we might take up, say, half a dozen 
constitutional diseases such as we have to meet 
every day, and reiterate some opinions which seem 
to establish that the endocrine element in these is 
prominent (in varying degree depending upon the 
physiological substratum of the individual and 
their reactivity to the fundamental causes of dis- 
ease) and, therefore, of no mean clinical im- 
portance. 

I propose to refer to rheumatism, epilepsy, neu- 
rasthenia, diabetes, tuberculosis and syphilis; and 
though each is a subject worthy of a comprehens- 
ive discussion, I will gather together some hints 
which I hope may remain with you after this meet- 
ing is over: 

Rheumatism is "a, constitutional disease with lo- 
cal manifestations." Some say that it is due to an 
infection, others to uric acid, still others to acid- 
osis. Each may be correct, for there are almost as 
many forms of rheumatism as there are rheumatic 
patients. If it is an infection with the s. rheumat- 
icus or other microorganism, the thyroid, as an im- 
portant part of "the powers of resistance" of the 



22 THE INTERNAL SECRETIONS 

body^ is concerned. If it is a toxemia the adrenals 
must be influenced in some way, for of all the or- 
gans in the body, endocrine or otherwise, the ad- 
renals are the most susceptible to toxins — they re- 
act on the slightest provocation, and are largely re- 
sponsible for the well-known sympathetic mani- 
festations of toxemia. 

The thyroid is more often implicated than any 
other endocrine organ, and subthyroidism many 
times is the one and only cause of what is supposed 
to be rheumatism. The sluggish metabolism of the 
rheumatic is so nearly like that of the cretin or 
myxedematous patient (and responds equally to 
indicated treatment) that I believe the French 
(Gauthier, Gilbert, Carnot and Leopold Levi) are 
right in emphasizing thyroid dyscrasia as an actual 
cause of "rheumatism.'' (3) 

As one acquires the habit of considering rheuma- 
tism from this angle, it is surprising how many of 
the clinical signs of thyroid insufliciency are dis- 
covered. And it is equally true that attempts to 
control these associated manifestations, often si- 
multaneously benefit the more decidedly rheumatic 
symptoms. 

Whenever you meet rheumatism, especially the 
chronic forms, at least think of the thyroid and its 
possible relations to it. 

Epilepsy is one of the profession's ''hardest nuts" 
and is not "easy to crack." Probably there are fac- 
tors involved that we know very litle about as yet, 



! 



IN PRACTICAL MEDICINE 23 

such as the presumed bacillus epilepticus, the ef- 
fects of allergy and the cause and effects of the cer- 
ebral edema which seems to be present. Many 
clinicians have discovered threads connecting epi- 
lepsy with the endocrine glands — the thyroid has 
long since been supposed to play some part in some 
cases, "^ the parathyroids are implicated in many 
other convulsive conditions, perhaps also in epi- 
lepsy. Just a few weeks ago H. A. Knox (4) in a 
paper on ''Research in Epilepsy" reports fairly 
good results in 30 cases of epilepsy which were 
treated with desiccated parathyroids (2 grains 
three times a day, increasing each dose by 2 grains 
each month) and calcium lactate (1 dram of the 
saturated solution daily). The adrenals are played 
upon so invariably by the alimentary toxemia, the 
most prominent of all the findings in the disease, 
and so progressive a man as Cotton of the New 
Jersey State Hospital, of Trenton, is treating scores 
of cases (69 were recently reported) by keeping 
this particular relationship in mind. (5) 

Perhaps the gland that is receiving the most at- 
tention at present is the pituitary, and it seems to 
be affected more than rarely and, too, pituitary 
feeding is reported to have proved very useful (6) 
and several personal experiences confirm this. Suf- 
fice it to say that the glands of internal secretion 



*The subject of the relationship of the thyroid gland to 
epilepsy is more fully discussed in a recent paper by the author. 
(See Chapter XII.) 



24 THE INTERNAL SECRETIONS 

are so often involved in epilepsy that they are our 
most promising field of present research in unrav- 
eling the mysteries of this disease. 

Whenever you have to treat epilepsy, don't for- 
get the glands of internal secretion. To do this 
may alter your treatment in a most salutary man- 
ner. 

Neurasthenia has been called a "cloak v^ith 
which to cover slipshod diagnoses" — scientifically 
speaking, there is really no such thing. But the 
patient won't believe this, for something is cer- 
tainly wrong when they are supposed to have "neu- 
rasthenia" and that "something" is of a chemical 
rather than a nervous character. Cannon's work 
on the relations of the emotions to adrenal activity 
is destined to clear up many of our hazy concep- 
tions of functional pathology. It is a big subject 
and Cannon has written a whole book on it; (7) 
but it must suffice to say that neurasthenia really 
seems to be nothing more nor less than a mani- 
festation of functional dysadrenia. Permit me to 
read you two quotations* before we leave this: 

"The typical neurotic generally has, if not al- 
ways, disturbance of the thyroid gland. The typi- 
cal neurasthenic probably generally has disturb- 
ance of the suprarenal glands on the side of insuffi- 
ciency. The blood pressure in these neurasthenic 
patients is almost always low for the individuals. 



*The second quotation 9 (from Kinnier Wilson's writings) 
will be found on page 89 of Chapter VII. 



IN PRACTICAL MEDICINE 25 

and their circulation is poor. A vasomotor paraly- 
sis, often present allows chillings, flushings, cold 
or burning hands and feet, drowsiness when the 
patient is up, wakefulness on lying down and hence 
insomnia. There may be more or less tingling or 
numbness of the extremities." (9) 

Whenever you encounter a neurosis, try to fix 
connecting links between it and the endocrine 
glands ; and you may succeed more times than you 
will fail. 

Diabetes is an endocrine disease — that is, if we 
believe that the pancreas has an internal secretory 
function as the physiologists have most conclu- 
sively shown. The so-called Allen treatment not 
merely reduces toxemia (which excites the ad- 
renals) but saves the pancreas (which is antagon- 
ized by the adrenals) and thus "acts both ways." 
The successful treatment of functional diabetes 
mellitus — not that form of the disease which is due 
to serious structural change as in the diabetes of 
youth, cancer of the pancreas, etc. — embodies three 
things: (1) relieving the pancreas of as much work 
as possible, (2) increasing the pancreatic internal 
secretion if this be feasible, (3) removing toxemia 
and modifying the nervous circumstances (stress, 
worry, mental fatigue), thereby reducing adrenal 
excitability. 

Tuberculosis is never a local affair; it can not be. 
Hence the general reaction, whether toxic, febrile, 
afebrile or nutritional, or all of these combined, also 



26 THE INTERNAL SECRETIONS 

affects the endocrine glands for they are a part of 
the body, and, in fact, they are the most sensitive 
part of the body. 

It is strange that as yet only a few men, of whom 
Dr. Pottenger here is probably the most aggres- 
sive, are taking this fact into consideration. We 
have such a big fight on our hands that all we can 
see is hygiene, diet and tuberculin. Now all of 
these are splendid, but why not seek out the 
changes of chemistry due to the effects of the tu- 
berculosis on the endocrine glands? Are there no 
evidences of endocrine involvement? For instance 
in long drawn out chronic disorders asthenia is uni- 
formly present, why not endocrinasthenia? This 
new word has heretofore been called *'pluriglandu- 
lar insufficiency" and it represents an almost uni- 
versal concomitant of tuberculosis. 

We must not forget to mention the frequency 
with which the picture of dysadrenia is prominent 
— hyperadrenia is common, with the circulatory 
irritability, heart excitement, alimentary spasm 
and occasional digestive crises. Later hypodrenia 
is invariably present with asthenia plus, subnormal 
temperature, low blood pressure and deficient sym- 
pathetic tone. 

I am not saying that the appreciation of these 
endocrine features of tuberculosis is going "to 
revolutionize our conceptions of this disease," but 
I do say this : 

When you see tuberculosis remember "endocrin- 



IN PRACTICAL MEDICINE 27 

asthenia'' and if direct measures are taken to offset 
this phase of the symptomatology of tuberculosis, 
surely no harm will have been done. 

Syphilis — the great toxemia, is probably re- 
sponsible for more organic or structural diseases 
than any other single cause. And what is true 
with bone, nerve, muscle and, in fact, all tissues, is 
equally true of the endocrine glands. Many a pitu- 
itary tumor or brain condition influencing this 
gland is of luetic origin. Many a "hidden syphilis'' 
is insidiously affecting function and this does not 
miss the endocrine glands even if it may not be 
causing actual structural change in them. 

I am convinced that at least a part of the consti- 
tutional manifestations of syphilis, and especially 
those which may be connected with the sympa- 
thetic nervous system, are directly the result of 
endocrine changes resulting from the toxic effects 
of this infection. 

We know that syphilis has the peculiar capacity 
of wreaking its vengeance on the innocent; and 
fully one half — I am speaking offhand — of inher- 
ited endocrine defects, functional or organic, are 
traceable to syphilis.* The feeble minded, the de- 
fectives, the incompetents and many who may not 
be so decidedly marked, but none the less have a 
facility for functional derangements — whose con- 



*This is probably an overstatement, though lues is certainly 
a universal scourge; and is often a factor in ductless glandular 
troubles. 



28 THE INTERNAL SECRETIONS 

stitutions are ''not right" — in reality may be suffer- 
ing from the inherited defects caused by syphilis.* 

Whenever you discover syphilis, look for its 
chemical effects — the functional pathology that it 
so often causes and, too, v^henever you find well- 
defined organic endocrine disease think at once of 
syphilis and keep on thinking of it until it is ruled 
out, or no longer a question. 

In closing I w^ill take this excellent opportunity 
to offset a tendency to discount statements v^hich 
seem to indicate that I "see ductless glands in 
every case," as one man put it the other day, by 
reminding you that there are ductless glands in 
every case ! I will supplement this by adding that 
they are very important and responsible little or- 
gans, for not only do they serve the body and suffer 
with the body; but when their first pathology is 
discovered and suitably treated, a new aspect many 
times is put upon a case. 

REFERENCES 

1. Editorial, "Functional Medicine," New York Medi- 
cal Journal, 1916, civ, 1155. 

2. Editorial Note, "A Therapeutist's View on Cancer." 
Am. Jour. Clin. Med., 1917, xxiv, 181. 

3. narrower, Henry R., "The Relation of the Internal 
Secretions to Rheumatism," etc. Amer. Med., 1915, xxl, 363. 
(This is Chapter XI of this book.) 

4. Knox, H. A., "Research in Epilepsy." New York 
Med. Jour., 1917, cv, 406. 



*This does not necessarily mean that the unfortunate actu- 
ally has inherited syphilis, although it is too often discoverable 
by our present methods of clinical research. 



IN PRACTICAL MEDICINE 29 

5. Cotton, H. A., et al, "The Pathogenesis and Treat- 
ment of Epilepsy." New York Med. Jour., 1916, civ, 532. 

6. Editorial, "The Prospects of Anterior Pituitary- 
Therapy." Endocrinology, 1917, i, 13. See also Joughin, 
J. L., "Glandular Therapy and the Epileptic Syndrome," 
New York Med. Jour., 1916, ciii, 693; and Tucker, B. R., 
"The Relation of Hypopituitarism and Epilepsy." Va. Med. 
Semi-Monthly, 1916, xxi, 1. 

7. Cannon, W. B., "Bodily Changes in Pain, Hunger, 
Fear and Rage." New York, 1915, Appletons. 

8. Editorial, "Neurasthenia — Suprarenal Insufficiency," 
Jour. A. M. A., 1915, Ixv, 2166. 

9. Kinnier-Wilson, S. A., The Clinical Importance of 
the Sympathetic Nervous System," London, 1913. See also 
narrower, Henry R., "The Adrenal Glands and their Sig- 
nificance in General Practice." Med. Rev. of Reviews, 1917, 
xxxii, 335. (This is Chapter VII of this book.) 



IV 

THE INCONSPICUOUS, EVERY-DAY 
FORMS OF THYROID INSUFFICIENCY 

THE so-called "minor thyroid insufficiency'' oc- 
curs in the routine work of every physician, every 
day. Very often it is entirely overlooked. It is the 
principal cause of quite a number of widely varying 
conditions and a factor of importance in many 
others. The thyroid gland has been aptly called 
"the keystone of the endocrine arch"; and we are 
beginning to realize that the glands of internal se- 
cretion play a much more important role than 
many of us had hitherto imagined. In fact, they 
are the prime factors in the regulation of metabo- 
lism; dominate the nervous system, more especially 
the sympathetic; and are altogether indispensable 
to the maintenance of the physiologic harmony of 
the body. 

Our interest in these glands, then, by no means 
should be limited to the mere consideration of defi- 
nite disease in one or more of them. We should 
seek rather to appreciate the insidious and insig- 
nificant minor aberrations from the normal, and in 
so doing in many cases we will be able to forestall 
the more serious organic manifestations which 
later assert themselves. (My use of the word "in- 



Read before the Riverside County Medical Society, De- 
cember 13, 1915, and reprinted from the California State Jour- 
nal of Medicine (San Francisco), May, 1916. 

(30) 



IN PRACTICAL MEDICINE 31 

significant" refers rather to the ease with which 
these conditions are appreciated, than to their com- 
parative importance, for these aberrations are cer- 
tainly much more important than yet appears to 
many physicians.) 

As we occupy ourselves in searching for the 
early, minor manifestations of internal secretory 
disturbance, we will be able not merely to forestall 
the more serious organic diseases, but will discover 
that unsuspected associated symptoms, from chil- 
blains to nocturnal enuresis, or rheumatism to mel- 
ancholia, will be modified by organotherapeutic 
measures which may have been directed at some 
entirely different condition. 

Most of our practical information on this sub- 
ject has been acquired accidentally. A physician is 
investigating a certain train of symptoms and he 
casually glimpses something he had not been look- 
ing for; or some concomitant condition at which he 
had not been especially directing his efforts, is 
cleared up and a new therapeutic procedure is born. 
Such experiences have laid the foundation for prac- 
tical organotherapy, and while this form of thera- 
peutics is often altogether empirical, we are or 
should be thankful that we can bring about results 
that are nothing short of marvelous, even though 
we cannot quite explain the ''how" or the ''why." 

When the functions of the thyroid gland were 
just beginning to be appreciated some 25 years ago, 
most of those who studied the matter did so from 



32 THE INTERNAL SECRETIONS 

the standpoint of the influence upon the organism 
of the absence, either congenital or experimental, 
of this gland. A year or two later, when Murray, 
then of Newcastle, first administered a preparation 
of animal thyroids, he gave it to a woman suffering 
from myxedema, and for a long time thyroid ther- 
apy was confined to the serious major thyroid syn- 
dromes. Both these circumstances have tended 
to obscure the question of the less obvious thyroid 
disorders, and for a long time the use of this new 
remedy was limited to the treatment of those cases 
in which there was a marked affection or entire ab- 
sence of the organ. 

An important result of this still persists. Until 
quite recently the generally recommended dose of 
thyroid was altogether too large, at least, in the 
majority of the cases in which it is to be given. 
This was doubtless due to the fact that the original 
dosage as indicated in the various pharmacopeias 
was based upon experiences in the treatment of 
athyroidic individuals. It is true that a commonly 
suggested dose — five grains three times a day- 
may be none too much for myxedema or cretinism. 
Occasionally it may be increased advantageously 
above this figure, for in organotherapy "there is no 
dose save dose enough" — the only difficulty being 
how to determine when "enough'' is given; but 
since we are now using thyroid in a host of other 
disorders related to functional minor hypothyroid- 
ism we must begin with much smaller doses, say 



IN PRACTICAL MEDICINE 33 

an average of one-quarter or one-half a grain three 
times a day. 

This has had an unfortunate influence upon the 
practical consideration of this subject. Our atten- 
tion having been directed to an important series of 
facts, we have overlooked much else that is of 
greater importance in every-day medicine. After 
all, the major thyroid insufficiencies are not so very 
common. We see them occasionally and usually 
they interest us only moderately, for the treatment 
is now fairly w^ell understood and there is little to 
do save to follov^ the v^ell-established procedures 
and supply the lack that nature or the surgeon ac- 
cidentally has brought about. On the other hand 
the minor cases of hypothyroidism complicate the 
work of the general practitioner in such disorders 
as nocturnal enuresis, headache, cold feet and 
hands or chilblains. The dermatologist is con- 
cerned because of the connection of hypothyroid- 
ism with many dermatoses, such as psoriasis, pru- 
rigo, eczema or herpes. The internist finds a rela- 
tion between this condition and certain forms of 
rheumatism and cardiac disorders. The neurolo- 
gist knows that neurasthenia, melancholia, many 
forms of insanity and some of the psychoses may 
be purely thyroid in origin and as one prominent 
alienist once put it, "the most important single 
remedy in the asylum is probably thyroid extract.'' 
The gynecologist finds the thyroid a direct cause of 
many functional genital conditions and has learned 



34 THE INTERNAL SECRETIONS 

that it is so intimate with the ovaries that disorders 
of them cannot occur without some reflex influence 
upon thyroid activity, he also has found in thyroid 
extract a most useful means of treating many 
forms of female disease, especially amenorrhea and 
dysmenorrhea of certain forms. The surgeon finds 
the thyroid more of an unmitigated nuisance than 
a help, although a connection between thyroid ac- 
tivity and bone growth is reported and the con- 
trol by this gland of development makes it of im- 
portance in the consideration of a number of de- 
formities and dystrophies. Last, but not least, in 
pediatric practice thyroid therapy, and of course 
the physiologic influence of this gland, is all im- 
portant; and thyroid extract is one of the most 
commonly used organotherapeutic remedies in the 
treatment of many infantile disorders. We have 
already mentioned its possible utility in nocturnal 
enuresis; and in many nutritional disturbances, 
most of which are of endocrine origin, the thyroid 
is the most commonly disordered gland. In fact, 
one can hardly find a nutritional dyscrasia in chil- 
dren without very quickly tracing a part of its 
origin, at least; to the thyroid gland. Such mani- 
festations as mental dullness, enlarged tonsils or 
adenoids, nasal or bronchial catarrh, dry, rough 
skin with coarse hair, as well as defective speech 
and occasionally soft bones, are all indications of a 
possibly deficient thyroid activity. The metabolic 
changes in rickets and marasmus are undoubtedly 



IN PRACTICAL MEDICINE 35 

partially due to disturbances in what Gauthier calls 
"the thyroid apparatus/' i. e., the thyroid, thymus 
and parathyroids; and it seems quite certain that 
the idea that this disease was due solely to faulty 
feeding or to the impossibility of breast feeding, 
must now be relegated to the background and the 
thyroid and associated glands be given first con- 
sideration. It is quite remarkable how very small 
doses of thyroid — one-twentieth to one-quarter 
grain three or four times a day for some weeks — 
will modify many of the manifestations just men- 
tioned — in adults as well as children. It is quite 
safe to say that the physician who remembers the 
extreme intimacy of the thyroid gland with dis- 
turbances of nutrition will be much more successful 
in their treatment. 

Apropos of this, an interesting statement by Isa- 
belle Thompson Smart of New York (Med. Rev. of 
Revs., 1915, p. 269) is worth quoting: ''The subtle 
influence (of thyroid) upon the hormone balance 
regulates in a mysterious way the whole of the in- 
ternal secretory activities. We cannot always ex- 
plain why thyroid extract is such a remarkable 
remedy, but we are satisfied to know the extraordi- 
nary results that frequently follow its use where 
there is a metabolic disturbance of obscure origin 
and in which there are none of the indications of 
cretinism. An unscientific but very satisfactory 
means of treating this large class of cases is to give 
thyroid extract, as one physician says, 'like a hit 



36 THE INTERNAL SECRETIONS 

in the dark/ and while misses are not uncommon, 
the physician who does this will be surprised at 
their comparative infrequency." 

When we recall the fact that the glands of in- 
ternal secretion are inextricably related to one an 
other and also that one cannot harm one without 
disturbing the harmonious interrelation of the 
others, the importance of this subject begins to 
grow upon us. Every-day circumstances such as 
the emotions, toxemia of alimentary and other 
origin, disease of all kinds, genital derangement of 
ever so slight a degree, especially in the female, 
and even the weather, may stimulate or depress, 
as the case may be, one or more of these hormone- 
producing organs with results which vary very de- 
cidedly in their clinical manifestations and seri- 
ousness. 

I cannot refrain from making the briefest ref- 
erence to a condition which has been aptly termed 
''the jerry-built constitution.'' The name is almost 
self-explanatory. By far the most important factor 
in such individuals is a thyroid instability. These 
individuals "catch everything," they are in a state 
of low metabolic activity, their urinary solids are 
low and the acidity is high. They are toxic. Neuras- 
thenia is common in such cases. They are none too 
bright in their studies or their business. They are 
the skim-milk of humanity, and how much of it 
there seems to be. Study the internal secretory 
capacity of such individuals ; enhance the action of 



IN PRACTICAL MEDICINE 37 

the thyroid, at the same time neutralizing the ten- 
dency toward acidemia and clean out the bowels, 
and there will be a metamorphosis that is some- 
times astonishing. Right here I want to say that 
the treatment mentioned exclusive of organother- 
apy is by no means so efficient and I have come to 
the conclusion that the hormones really do the 
work and the re-establishment of a normal alkalin- 
ity of the blood and the removal of as many of the 
toxic products as possible merely puts Nature in 
a position to respond to the stimuli to which she 
is accustomed and the lack of which is such a po- 
tent factor in the etiology of many of the cases 
mentioned. The detoxicating procedures are nega- 
tive treatment, if I may so term it; while the organ- 
otherapy is positive treatment. The former is good, 
for it gives Nature a chance; but both are better, 
because the hormones thus administered give Na- 
ture a boost. 

You realize, of course, that we cannot begin to 
consider the whole gamut of minor thyroid dis- 
orders to-night. Their ramifications extend into 
every phase of medicine. Leopold Levi and Baron 
Henri de Rothschild, of Paris, have written two 
fairly large books on this single subject; and in 
their most recent publication the relation of the 
thyroid to each of the important disorders, acute 
and chronic, is thoroughly discussed. Many dis- 
orders which we have mentioned incidentally are 
given the prominence of a chapter to themselves. 



38 THE INTERNAL SECRETIONS 

But before closing I would like to lend a little more 
emphasis to some points regarding diagnosis, as 
well as to the administration and dosage of thyroid 
extract. 

The diagnosis of minor hypothyroidism is com- 
paratively simple. Most often, I must admit, it 
is presumed to be present and "diagnosed'' by the 
therapeutic test. Several of the commonest symp- 
toms have already been mentioned and for conveni- 
ence it may be well to quote from a recent mono- 
graph by Lewellys F. Barker, of Baltimore, entitled 
"Some of the Commoner Types of Diseases of the 
Endocrine Glands": 

In examining children for minor hypothyroid- 
ism, three principal points should be kept in mind : 
(1) retarded growth; (2) habitual constipation, 
and (3) dullness in the schoolroom. In adults the 
most important symptoms are (1) endogenous 
obesity; (2) persistent constipation; (3) a dry, 
harsh skin; (4) subjective feelings of cold, and (5) 
recurring drowsiness in the daytime. Barker ad- 
vises the therapeutic test in all cases where there 
is any doubt of the presence of a condition of this 
nature; in other words, this eminent internist sug- 
gests recourse to empiricism, and he undoubtedly 
is right. 

Some other symptoms which have directed at- 
tention to a thyroid insufficiency which had been 
entirely overlooked, may be mentioned. They are, 
however, not infallible signs: Cracked and brittle 



IN PRACTICAL MEDICINE 39 

finger nails; loss of the outer third of the eye- 
brows; twitching or blinking of the eyelids; fleet- 
ing and indefinite joint pains; low total solids in 
the urine; sensitiveness to cold and especially the 
need for an unduly large quantity of bedclothes; 
snoring (without other good reasons therefor) ; re- 
duced resistance to infections, especially of the 
skin, as acne, etc. To these must be added the 
well-known symptoms of major hypothyroidism, 
though, of course, in the "minor" cases they are not 
so well marked. 

Thyroid extract is a most useful remedy and like 
most drugs of its importance is worthy of much 
more study and far greater clinical application. 
Small dosage is always the rule. A quarter of a 
grain is my usual initial dose. It may be repeated 
from two to six times a day. Rarely is it necessary 
to give more than three grains a day in divided 
dosage. Occasionally one meets a patient who 
needs thyroid but cannot tolerate it; in such cases 
it is well to try giving the whole day's dose, not 
more than one-half grain at first, increasing later 
to one and one-half or two grains, at bedtime. This 
obviates some of the inconveniences with the heart 
and respiration. In this class of cases Heinrich 
Stern, of New York, gives sodium cacodylate in 
small doses with the thyroid. He finds that this 
mitigates the inconveniences of an idiosyncrasy to 
this remedy. 

Thyroid must be given for some time to be most 



40 THE INTERNAL SECRETIONS 

effective. The French method appeals to me most. 
They give, say, one centigram (one and one-half 
grains) of thyroid per day, divided into three or 
more doses, and continue thus for one week. The 
drug is then omitted for a v^eek or even longer, 
and then begun again for another period of a week, 
using the same or a slightly larger dose, then omit- 
ting it for another week or more, and so on. Occa- 
sionally individuals supersensitive to thyroid medi- 
cation may establish a tolerance to a given dose, 
and after reducing the amount and starting again, 
it may be found that they are able to take very 
much larger doses with none of the previous symp- 
toms of intolerance. 

In many cases where thyroid is indicated, espe- 
cially in obese women who are taking thyroid to 
facilitate reduction, pluriglandular therapy may be 
helpful. Corpus luteum given with the thyroid is 
sometimes of much assistance, especially in neuras- 
thenic women and those at or near the menopause. 
In asthenic cases with a considerable degree of 
muscular weakness and constipation pituitary is 
given in conjunction with thyroid with good re- 
sults. 

Pituitary (whole gland) is often given advan- 
tageously with thyroid in children who have hypo- 
thyroidism. This is especially so in cases with mal- 
development and dullness. The dose may consist 
of one-quarter to one-half grain with half as much 
thyroid three or four times a day. The amount of 



IN PRACTICAL MEDICINE 41 

pituitary may be increased more frequently than 
the thyroid, giving finally, say, two and one-half 
or more grains of pituitary and one-half grain of 
thyroid at a dose. 

An important point regarding the dosage of thy- 
roid in children is the fact that the amount given 
is not regulated by the body v^eight or age of the 
child. Dosage depends solely upon individual sus- 
ceptibility. The only w^ay to establish a suitable 
dose for a given case is to start with a small dose, 
say, one-tenth or even one-twentieth of a grain at 
the usual intervals, giving increased doses very 
carefully until evidences of intolerance are noted. 
Then stop the medication for a period and recom- 
mence again with the previous dose or slightly less. 

An important point to which I have never seen 
attention drawn concerns the label-dosage of sev- 
eral thyroid preparations on the market. Prepara- 
tions of this character are usually given in tablet 
form, as it is most convenient and quite satisfac- 
tory. Manufacturers indicate the contents of their 
tablets in three ways on the labels: (1) 5-grain 
tablets; (2) 5-grain tablets, each tablet represent- 
ing 3 grains of desiccated thyroid substance, and 
(3) tablets representing 5 grains of fresh thyroid 
glands. These figures are mentioned merely for 
convenience, since 5-grain tablets of thyroid are 
not used so much these days. It will be clear that 
(1) does not contain 5 grains of the active remedy 
of thyroid with no excipient to bind it or to facili- 



42 THE INTERNAL SECRETIONS 

tate its rapid disintegration. I much prefer the 
second way of expression, the size of the tablet is 
merely for manufacturing convenience and the 
amount of active constituent is definitely stated. 
Regarding (3) I cannot understand why a firm 
should insist on denoting the amount of fresh sub- 
stance, rather than the standard (U. S. P., in this 
particular instance) preparation of dried gland. 
This may be the cause of trouble. For instance: A 
physician is giving a Parke, Davis & Co. tablet, 5 
grains at a (hypothetical) dose. For some reason 
or another the treatment is continued with a Bur- 
roughs, Wellcome & Co. tabloid, but it is not no- 
ticed that "Tabloid Thyroid Gland Gr. 5" repre- 
sents fresh substance, or only one-fifth as much of 
the dried gland as had been previously given! To 
reverse this experience would be much worse, for 
then a change of brand would entail a sudden mul- 
tiplication of the desired dose by five ! Parenthet- 
ically it may be remarked that this last-mentioned 
firm puts a ''Tabloid Thyroid Gland Gr. 1-10,'' 
which contains only one-fiftieth of a grain of the 
dried gland. 

There is a good deal more, but it will have to 
be left for another time. Sufiice it to say that minor 
thyroid insufficiencies are as common in the aver- 
age run of patients as orange trees are here, only 
they are not always so obvious. 

Let us cultivate our sense of discernment so that 
cases of this kind will not slip by unnoticed again. 



V 

PLURIGLANDULAR INSUFFICIENCY: ITS 
INCIDENCE AND TREATMENT 

PLURIGLANDULAR insufficiency, or hypo- 
endocrinism, is a comparatively recent term, rarely 
found in the medical literature published seven or 
more years ago. To appreciate the full import of 
the subject which has been allotted to me, it is nec- 
essary, first, to realize the fact that the endocrine 
system is a very essential part of the organism, 
since by its various internal secretions practically 
the v^hole of the workings of the body are regu- 
lated and correlated. It might be compared to the 
magneto of the automobile or, perhaps, to the ex- 
change of a telephone system. 

In his comment in the New York Medical Jour- 
nal (1) on the advanced position taken by a Com- 
mittee appointed by the Congresso della Societa 
Medica Italiana in 1912, the editor says: "One can- 
not but be impressed by the vast field which the 
ductless glands have steadily invaded, in keeping 
with the conclusions announced nearly ten years 
ago, in this country, that these organs were second 
to none in the body in their bearing upon physiol- 
ogy, pathology, and clinical medicine." The Com- 
mittee representing these Italian investigators in 
their official report to the Congress (2) asserted 



Prepared for a "Special Internal Secretions Number" of "The 
Practitioner" (London), published January, 1915. 

(43) 



44 THE INTERNAL SECRETIONS 

that: 'The internal secretions manifest an influ- 
ence upon the anomalies of growth, morphology, 
and organic metabolism; on nutrition and inherent 
excitability of the nervous system; on resistance to 
infections and intoxications, as well as a prepon- 
derating role in the causation of dyscrasias and 
morbid temperaments." They also conclude that 
the equihbrium of the nervous system, the sympa- 
thetic in particular, may be regarded as maintained 
by the internal secretions and that in nervous dis- 
eases per se they act probably as indirect or predis- 
posing factors. 

The active principles of these internal secretions 
are now generally called hormones, and we are be- 
ginning to realize that they are a factor of extreme 
importance in the regulation of metabolism. In the 
body every motive force is balanced by a retarding 
force and this nice balance is essential to health; 
hence if one or another of these factors gain the 
ascendency, or is diminished in activity, disorgan- 
ization must naturally result and the extent of this 
disorganization can hardly be confined to the single 
area in which it is initiated. 

The intimate relations of the secretions of the 
various endocrine organs predicate pluriglandular 
disturbance as the result of an initial monoglandu- 
lar disorder, thus explaining the dictum of Bayard 
Holmes (3) : ''During the past year much evidence 
has accumulated to show that diseases of the duct- 
less glands are usually plural rather than isolated 



IN PRACTICAL MEDICINE 45 

and single. Pluriglandular disease is the rule rather 
than the exception." 

This position is substantiated by Mullaly (4), 
who states that from a study of the autopsy records 
at the Royal Victoria Hospital, Montreal, "In the 
infrequent autopsies in cases of ductless gland dis- 
orders pathological changes were observed in more 
than one of the ductless glands." 

Functional disorders of many varieties may be 
either directly due to, or intimately associated with, 
changes in the various hormone stimuli which are 
so essential to the maintenance of the chemical bal- 
ance upon which the intricacies of metabolism de- 
pend. Many of these disorders are already included 
in our present-day classification of disease and are 
considered among the ''disorders of the internal se- 
cretory glands": in most of these cases, however, 
the disturbance is prominent in one of the glands, 
and among these we recall thyroid insufficiency, 
the major form or myxedema and the minor form, 
sometimes known as Hertoghe's syndrome (myxe- 
deme fruste), adrenal insufficiency or Addison's 
disease, Langerhansian insufficiency or pancreatic 
diabetes, parathyroid insufficiency or tetany, and 
numerous other disorders of function resulting 
from disturbance in the internal secretory activi- 
ties of the gonads, hypophysis, epiphysis, etc. 

Harry Campbell, in his masterly study of the role 
of the blood plasma (5) rightly intimates that the 
blood plasma carries a host of varying chemical 



46 THE INTERNAL SECRETIONS 

messengers or hormones whose balance is essential 
to the proper regulation of the numerous bodily 
functions. This explains why the normal content 
of the chromaffin principle does not exert the same 
action as when a dose of adrenalin is administered 
— in the normal amounts in which it is found in 
the blood it is balanced by the Langerhansian prin- 
ciple. 

Campbell considers that cell activity is properly 
divided into the egoistic and the altruistic cell func- 
tions. The former consists in the maintenance of 
individual cell activity, while the latter concerns 
the supply to the organism as a whole of certain 
services, probably brought about by the hormones, 
such as are exemplified in the numerous functional 
relationships between organs. This so-called "al- 
truistic" function is of extreme importance, for the 
cell itself may seem to all intents and purposes 
quite healthy and yet still gravely fail in its altru- 
istic functioning — a failure which, small though it 
be, may suffice to disorganize the delicate hormonic 
balance. A consideration of these complex inter- 
relations* will establish the extreme importance of 
the hormone equilibrium, and, of course, its disturb- 
ances. 

There are two forms of endocrine disorder — or- 
ganic and functional. The former, fortunately rare, 



*Por a fuller discussion of this question, see Chapter III, 
"The Hormone Balance," in Practical Hormone Therapy (Bail- 
liere), by the writer of this article. 



IN PRACTICAL MEDICINE 47 

is usually diagnosed only when the changes are 
permanent; it is, therefore, very difficult to treat 
satisfactorily. The latter, on the other hand, is 
extremely common, it is frequently overlooked, 
and, when its presence is appreciated and put under 
treatment, it responds in an encouraging way. 
Hence the principal effort of the writer will be to 
emphasize the frequency and importance of func- 
tional insufficiencies of the endocrine organs, rather 
than the definite organic diseases of these glands. 
One can, however, advantageously refer, in pass- 
ing, to several important papers and case reports 
which outline the pathology of those serious or- 
ganic conditions which combine to form the "plu- 
riglandular syndrome." 

One of the most pronounced cases of organic 
pluriglandular disease was recently reported by 
Maase, (6) the essential facts being briefly recapit- 
ulated here: The patient was a Russian girl aged 
24, with an epileptic and diabetic ancestry. Normal 
in every way till 18, she then developed ophthalmo- 
plegia. At 20 she developed a myxedematous state 
attended by suppression of the menses. Glycosuria 
was found and a positive Wassermann reaction; 
later a spinal curvature was discovered. There was 
a shrinkage in the body measurements represented 
by various deformities. The bone condition some- 
what resembled osteomalacia. Death occurred un- 
expectedly from erysipelas. At the autopsy the 
hypophysis, normal in size, was adherent to the 



48 THE INTERNAL SECRETIONS 

bone and of firm consistence. Thymus remains 
were quite abundant, while the thyroid was abnor- 
mally small in both lobes. The pancreas was small, 
consisting largely of fat and connective tissue. The 
ovaries were abnormally small and showed no 
Graafian follicles. The bones were much thinned 
and brittle, the liver was fatty. The adrenals alone 
of all the endocrine glands seemed to be normal, 
so that the case may be termed subtotal or hypo- 
endocrinism. The other organs were normal, save 
that the heart exhibited the changes to be expected 
after death from erysipelas. 

In the Italian medical literature of the past year 
Consolazio, (7) Bianchi, (8) and Zilocchi (9) have 
contributed interesting monographs on this sub- 
ject. In France, Costa (10) and Rebattu (11) have 
discussed this subject, and Parhon and his associ- 
ates (12) have experimentally produced conditions 
in animals allied to the pluriglandular syndrome. 
All of these communications consider the serious 
organic conditions, and while there is undoubted 
advantage in studying this phase of the subject, it 
is of far less immediate practical value than the 
consideration of the much more frequent functional 
disturbances which, because of their insidious on- 
set, frequently are entirely overlooked. 

Costa (10) states that nice distinctions between 
conditions due to the various ductless gland dis- 
orders are very difBcult to make, since the internal 
secretory glands all have an action on the develop- 



IN PRACTICAL MEDICINE 49 

ment of the skeleton, on nutrition, and also a pres- 
sor or depressor action on the circulation. He does 
not attempt the differentiation suggested by Claude 
and Gougerot, (13) Gandy, Deseglise, and others, 
to determine in which gland the hypofunction pre- 
dominates and which is essentially responsible for 
the disturbance. This undertaking appears to him 
much too difficult at present. In Costa's case, how- 
ever, the discovery of the cause was made by the 
Wassermann test and antisyphilitic treatment 
caused a marked change for the better. 

The majority of the serious organic disturbances 
of the ductless glands seem to be syphilitic in ori- 
gin. The case reported by Costa above was luetic. 
In Maase's case, which has already been quoted, 
there was a positive Wassermann reaction, and de 
Moraes and Pernambuco, (14) in considering the 
relation of the pluriglandular syndrome associated 
with dementia precox in a girl of 19, established the 
cause as inherited syphilis. They found that the 
ovaries, thyroid, adrenals and mammae were si- 
multaneously affected. 

The only reason that we study disease is that we 
may be able the better to appreciate its influence 
and satisfactorily treat it, so the consideration of 
pluriglandular insufficiency would be incomplete 
without reference to the treatment of these condi- 
tions. 

The natural corollary of pluriglandular insuffi- 
ciency is pluriglandular therapy, and the most 



50 THE INTERNAL SECRETIONS 

practical consideration of this subject concerns the 
comparatively recent form of therapeutics which 
the knowledge of the influence of hypoendocrinism 
has made possible. 

It is altogether possible that the change of air 
ordinarily recommended to convalescents and in- 
valids, sanatorium treatment and other hygienic 
regimens, are beneficial largely because of the in- 
creased activity of the secretory capacity of all the 
glandular organs and it seems that the tonic phys- 
ical measures, such as hydrotherapy, electricity, 
massage, etc., are useful in part at least because 
they stimulate the endocrine organs to produce 
their vital messengers. In fact, Nogier (15) has 
suggested a special line of treatment with the hope 
of specifically exciting the internal secretory or- 
gans by physical methods, just as these methods 
are used to stimulate other functions, thus materi- 
ally modifying the conditions due to hypoendocrin- 
ism. This may be good, but to my mind cannot be 
compared with the more direct organotherapeutic 
methods. 

The most natural means to favor internal secre- 
tory activity are the products of the internal secre- 
tory glands themselves. Hallion's law is the funda- 
mental basis of scientific organotherapy. It is as 
follows : ''Extracts of an organ exert on the same 
organ an exciting influence which lasts for a longer 
or shorter time. When the organ is insuflicient, it 
is conceivable that this influence augments its 



( 



i 



IN PRACTICAL MEDICINE 51 

action, and, when it is injured, that it favors its 
restoration." 

One of the most important statements on the 
hormones is found in Starling's monograph on 
"The Chemical Co-ordination of the Body Func- 
tions." (16) This eminent authority confidently 
states his belief that "if the mutual control of the 
body be largely determined by the production of 
definite chemical substances in the blood, the dis- 
covery of the nature of these substances must en- 
able us to interpose at any desired place in these 
functions, and by this means to acquire an absolute 
control over the working of the human body. Such 
a control is the goal for which medical science must 
ever strive." 

Possibly, the not infrequent cases of seeming 
monoglandular disorder which do not respond to 
the orthodox treatment whether organotherapeutic 
or otherwise, might be more responsive to our ther- 
apeutic efforts if the fact that pluriglandular dis- 
ease is much more common than monoglandular 
disease was considered, and the administration of 
suitably combined extracts was substituted for the 
present thyroid, pituitary, adrenal, ovarian or other 
single extracts which may seem to be the proper 
treatment. 

It is quite certain that this subject, now on the 
verge of our present knowledge, before many 
years have passed will be taken into careful con- 
sideration by the general practitioner as well as the 



52 THE INTERNAL SECRETIONS 

internist, and the hormone balance will be a factor 
which is more thoroughly appreciated. It is true 
that the goal referred to in Starling's quotation is 
still far distant, and we are a long way from ac- 
quiring "absolute control over the working of the 
human body,'' but there can be no reasonable deny- 
ing that the administration of certain organic ex- 
tracts makes possible a control over certain func- 
tional conditions that is not obtainable in any other 
way. 

For several years the writer has been studying 
the applications of various combinations of pluri- 
glandular extracts in pluriglandular insufficiencies, 
particularly in the so-called "run-down" condi- 
tions, where no easily demonstrated and positive 
evidence of any defective action of a gland or series 
of glands can be demonstrated. Such cases include 
many forms of neurasthenia and functional neu- 
roses, and it is obvious that in the majority of these 
cases there must be a disturbed endocrinism. It is 
hardly reasonable to suppose that in an individual 
with prominent manifestations of half-speed func- 
tion, such as constant fatigue on slight exertion, 
defective oxidation as evidenced by low urinary 
solids, nerves that are easily set "on edge," circu- 
lation that is poor, with cold, clammy extremities, 
and not infrequently reduced tension and ambi- 
tion, and mental powers much below par, that the 
production of the essential chemical messengers is 
not reduced just as are all the body activities. This 



IN PRACTICAL MEDICINE 53 

being the case, pluriglandular therapy not only 
serves to replace, in however slight degree, the 
missing secretions, but favors an increased produc- 
tion of them by the homostimulant action already 
referred to. 

Theoretically this sounds very plausible and 
practically it has been found to w^ork very nicely. 
Pluriglandular therapy is undoubtedly empirical, 
for in the class of cases under discussion at least, 
there is no definite proof as to w^hich of the duct- 
less glands is deficient and to what extent. For 
this reason it has been ridiculed by some who for- 
get that nine-tenths of our present therapeutics 
was at one time purely empirical, while a good 
share of it still has no positive scientific basis. A 
procedure that has secured results before may do 
so again, hence it is worth trying. This is the pres- 
ent position of pluriglandular therapy, and it is be- 
lieved that the successes already obtained are an 
earnest of what is in prospect. 

Several combinations of organic extracts have 
been tried experimentally, and from a considerable 
experience it seems that the really tonic principles 
of this character are to be secured from the pitui- 
tary body, thyroid and gonads. My experience has 
been limited to the use of combinations of the ex- 
tracts of the ductless glands which are known to 
have a tonic effect. Chief among these are the thy- 
roid, posterior lobe of the pituitary and gonads, and 
for the past two years I have used a preparation 



54 THE INTERNAL SECRETIONS 

called hormotone with excellent results in a variety 
of "run-down'' states, in some of which there were 
obvious disturbances of one or more of the ductless 
glands and in others in which this change was pre- 
sumed to be present though not so evident from a 
clinical standpoint. 

Leonard Williams, whose studies in this field are 
of considerable interest, reported to the therapeu- 
tical section of the Royal Society of Medicine (17) 
that he had found that while pituitary substance 
had given good results in those ''curious and indefi- 
nite conditions — neurotic or neurasthenic — which 
occur so frequently in moth-eaten maiden ladies 
who emerge from boarding houses to go to church 
— I do not know how it does it, but it makes them 
feel better — . . . . Since I have been using a 
mitrailleuse called hormotone I have had consider- 
able success in those cases just referred to as bene- 
fited by pituitary." Among the conditions which 
I have treated are neurasthenia (in men and wom- 
en), amenorrhea, sexual neuroses and impotence, 
as well as several cases in which the manifestations 
were not sufficiently marked to be definitely named 
— the "run-down'' conditions. 

This treatment is by no means a specific, and my 
percentage of good results is only between 60 per 
cent, and 70 per cent. I have seen no really bad 
effects, the only untoward eft'ects occasionally 
noted being a feeling of irritability and temporarily 
increased nervousness, which disappeared on re- 



IN PRACTICAL MEDICINE 55 

ducing the dose of hormotone and did not reappear 
when its administration was very gradually in- 
creased. 

In senile conditions and old age there is an in- 
variable pluriglandular insufficiency due to the pro- 
gressive decline in all the functions. Lorand, whose 
book on this subject (18) is practical as well as in- 
teresting, makes frequent reference to the value of 
organotherapy, and I must admit that, in a number 
of cases which have come to my attention, the com- 
bination previously referred to has seemed to re- 
kindle the vital fires. 

The advantages of pluriglandular therapy are 
essentially the advantages to be derived from the 
individual substances which are combined. Obvi- 
ously such combinations are made with their syner- 
gistic action in mind. I have personally used small 
doses of antagonizing extracts with good results, 
because it seems that each of the substances stimu- 
lates the corresponding organs, thus increasing the 
hormone content of the blood as a whole and 
strengthening the chemical messages which are of 
such vital importance. A point worth emphasis 
concerns the capacity of the individual organ to re- 
spond to the stimulus of the corresponding extract. 
It seems established that "the degree of stimulation 
exerted by the administration of the hormone-bear- 
ing substances is in direct ratio to the need for such 
stimulation, i. e., an extract is more efficient when 
a corresponding active principle is deficient in the 



56 THE INTERNAL SECRETIONS 

body than when present in normal amounts. Hence 
in a combination of several extracts the principal 
action is the one which is deficient; that is to say, 
the more it is needed, the more useful it is." (19) 

Before closing it is proper to mention several re- 
ports in the literature on various forms of pluri- 
glandular therapy. In addition to the treatment 
of the definite thyro-pituitary deficiencies with thy- 
rodi and pituitary extracts, as first suggested by 
Renon and Delille, (20) Starkey (21) has been 
treating certain nervous diseases with a combina- 
tion of thyroid, parathyroid, testis and ovary. 

In gynecological practice it is not uncommon to 
combine lutein with small doses of thyroid with 
advantage in conditions where lutein may be indi- 
cated. A combination of several extracts is given 
by McCready in children with defective endocrine 
development and it seems quite well established 
that combinations are more useful than single 
gland extracts — at least in this class of cases. 

Bazzochi (22) has used a combination of thyroid, 
thymus and spleen in pyloric cancer. In pharyn- 
geal carcinoma, Shirlaw (23) suggests the use of 
the preparation called "Tabloid three glands," each 
tablet containing a large dose of thyroid (6 grains) 
with the addition of small doses of adrenal and 
pituitary substances. Unquestionably in cancer 
there is a definite hypoendocrinism, and attempts 
to modify this, while possibly without specific ef- 
fect upon the cancer itself, may be of assistance in 



IN PRACTICAL MEDICINE 57 

modifying other conditions which cause inconveni- 
ence to the patient. "Cancer is essentially a dis- 
ease of nutrition — i. e., errors in nutrition, whether 
local or general, are the factors which permit of 
the implantation of cancer cells and the growth of 
the tumor. The ductless glands preside over nu- 
trition. Hence it is not unreasonable to suppose 
that there may be some relation between disturb- 
ances of the hormone balance and cancer, and, too, 
that there may be some prospect of therapeutic 
value in the treatment of this disease by organo- 
therapy." (24) Finally, Billard (25) has advocated 
a combination of the extracts of spleen, liver and 
pancreas as an adjunct remedy of possible helpful- 
ness in cancer. 

Altogether the possibilities of various pluri- 
glandular combinations are almost without num- 
ber, since, as Leonard Williams (17) has indicated, 
the mitrailleuse is seemingly more useful than the 
single rifle shot. 

Since this was written Little (26) has made an- 
other interesting communication on his study of 
cancer, and shows that not only must we consider 
the relation of the ductless glands and their dis- 
orders to cancer, but that the use of certain prod- 
ucts of these organs has a decided effect in favor- 
ing the response of the body to other treatment. 
He used extracts of the pancreas and adrenal cor- 
tex. Little's hypothesis has several important 
points which are worthy of repetition: The prob- 



58 THE INTERNAL SECRETIONS 

able origin of the growth is in a highly specialized 
cell or cells, which for some reason or other have 
undergone a retrograde metamorphosis to the 
point where the power of reproduction, common 
originally to all cells but lost in these highly spe- 
cialized cells, has reappeared. This reproduction 
of such reverted cells is caused by a relative hypo- 
function of certain ductless glands. The ductless 
glands at fault in each case have some vital relation 
to sugar metabolism or calcium metabolism or 
both. 



It is over two years and a half since the fore- 
going was prepared, and in that time I have had 
numerous opportunities to see how important is 
the appreciation of pluriglandular conditions. 
Nothing establishes one's faith in medicine, or any 
part of it, like clinical success. So I will amplify 
this chapter with two brief case reports, one with 
which I had to do personally and the other to 
which my attention was drawn by the late Dr. 
Wendell Reber of Philadelphia. 

When my address was given before the Riverside 
County Medical Society* Dr. D. C. Strong of San 
Bernardino, reported a case of pituitary cyst in a 
boy. This had been successfully punctured and de- 
compressed and the boy recovered from the neigh- 
borhood and pressure symptoms and was given 
pituitary gland with additional improvement. How- 



*See Chapter IV. 



IN PRACTICAL MEDICINE 59 

ever this did not last, and the lad's mentality and 
progress was about at a standstill when I heard of 
the circumstances. Naturally defective mentality 
reminds one of thyroid trouble, despite the proven 
pituitary disease, and I suggested that the pituitary 
feeding be continued and reinforced with the addi- 
tion of thyroid gland. This was done with astound- 
ing results, for the boy is now as bright as any of 
his schoolmates and an excellent student. Here, 
of course, the pituitary insufficiency was but a part 
of the complex, and the pluriglandular therapy was 
much more successful than the administration of 
the single gland alone. 

The other case was just as peculiar. Dr. Reber 
wrote me of this and has since reported the case in 
the New York Medical Journal (1915, ci, 392). 
A man came for treatment for a progressive blind- 
ness and for some reason or another was given thy- 
roid gland with no perceptible benefit. He then 
received pituitary gland in conjunction with the 
thyroid, with considerable benefit to his vision. 
Some time later the vision was again impaired and 
pituitary gland was given since it had been so ef- 
fective previously. It was a failure until it was re- 
called that he had taken both thyroid and pituitary, 
and thyroid was added. The benefit was as prompt 
as previously, thus giving fairly substantial evi- 
dence that thyroid alone and pituitary alone were 
practically inactive; but that the combination 
caused a change in conditions which allowed of a 



60 THE INTERNAL SECRETIONS 

re-establishment of the disorder under treatment. 

I am confident from many clinical experiences 
that cases in which, say, thyroid treatment is obvi- 
ously indicated, often will respond more satisfac- 
torily when further search is made for associated 
endocrine disorder and suitable pluriglandular 
medication is substituted. 

REFERENCES 

1. Editorial: ''The Clinical Relations of the Internal 
Secretions," New York Med. Jour., 1912, ii, 1183. 

2. "L'Endocrinologia nelle sue Cliniche Applicazioni," 
Clin. Med. Ital., Rome, 1913, Hi, 599; see also Ibid.^ 1912, 
li, 665. 

3. Holmes, B. : "The Glands of Internal Secretions,'' 
Lancet-Clinic, Cincinnati, 1914, cxii, 319. 

4. Mullaly, E. J. : "A Case Illustrating Ductless Gland 
Relationship," Can. Med. Assoc. Jour., Toronto, 1914, iv, 37. 

5. Campbell, H. : "The Role of the Blood-Plasma in 
Disease," Lancet, London, 1907, i, 313 et seq. 

6. Editorial note : "A Unique Case of Pluriglandular 
Insufficiency," Med. Record, New York, 1914, Ixxxv, 301. 

7. Consolazio, E. : "Sindromi Plurighiandolari," Gaz. 
Inter, d. med., Naples, 1914, xvii, 568. 

8. Bianchi, G. : "Osservazioni Istopatologiche su un 
Caso di Insufficienza Plurighiandolare Endocrina," Pathol., 
Genoa, 1914, vi, 74. 

9. Zilocchi, A. : "Importanza Patogenetica de TAppa- 
recchio Plurighiandolare," II Morgagni, Milan, 1913, Ix, 352- 
361. 

10. Costa, S. : "Syndrome d'Insuffisance Pluriglandu- 
laire," Paris Med., 1913, xi, 378. 

11. Rebattu, M. : "Syndrome Pluriglandulaire (Geni- 
to-Surreno-Thyroidien)," Lyon Med., Lyons, 1914, cxxii, 
605. 

12. Parhon, C. et al. : "Note sur les Syndromes Pluri- 
glandulaires experimentaux," Rev. Neurol., Paris, 1913, 
xxvi, 226. 



IN PRACTICAL MEDICINE 61 

13. Claude, H., and Gougerot, H. : "Syndromes Pluri- 
glandulaires : Delimitation des Syndromes d'insuffisance et 
d'hyperfonctionnement Pluriglandulaires," Gaz. d. Hop., 
Paris, 1912, Ixxxv, 849-897. 

14. de Moraes, P. V., and Pernambuco, P. : "Consid- 
erations regarding a Case of Pluriglandular Syndrome as- 
sociated with Dementia Precox," Arch, Brasileiros de Med., 
Rio., 1912, ii, 671. 

15. Nogier, Ph. : "L'excitation et la Frenation des 
Glandes Endocrines par les Procedes Physiques," Bull, de 
I'Acad. Sci., Paris, 1912. 

16. Starling, E. H. : "The Chemical Co-ordination of 
the Activities of the Body," Science Progr., London, 1906- 
7, i, 557. 

17. WilHams, L. : "Discussion on the Therapeutic 
Value of Hormones," Proc. Roy. Soc. Med. (Sec. Then), 
London, 1914, vii, 33. 

18. Lorand, A.: Old Age Deferred, 1911, F. A. Davis 
Co., Philadelphia. 

19. Harrovi^er, H. R. : Practical Hormone Therapy, 
1914, Bailliere, London, p. 424. 

20. Renon, L., and Delille, A.: "Sur les effets des 
extraits d'hypophyse, de thyroide, de surrenale, d'ovaire 
employes en injections intraperitoneales (simples et com- 
bines) chez le lapin," C. r. Soc. Biol., Paris, 1908, Ix, 1037. 

21. Starkey, F. R. : "The Combined use of Thyro- 
parathyroid. Pituitary, Ovarian, and Testicular Extracts," 
N. Y. Med. Jour., 1112, xcv, 1257. 

22. Bazzochi, A. : "Sulla Istoterapia del Tumori 
Maligni dell* uomo," Tumori, Rome, 1913, iii, 320. 

23. Shirlaw, J. T. : "The Nature and Origin of Can- 
cer," Brit. Med. Jour., London, 1911, ii, 1625; see also 
L'pool Med.-Chir. Jour., 1913, xxxiii, 398. 

24. Harrov^er, H. R. : Practical Hormone Therapy, 
1914, Bailliere, London, p. 422. 

25. Billard, M. : "Essai d'opotherapie Anticancereuse," 
Centre med. et pharm. (Gannat), 1909, xiv, 319. 

26. Little, S. W. : "A Further Study of Cancer," Bos- 
ton Med. and Surg. Jour., 1914, clxxi, 587. 



VI 

SHELL SHOCK ("NEURASTHENIA") AND 

THE INTERNAL SECRETIONS: WITH 

SUGGESTIONS AS TO TREATMENT 

THERE seems to be reliable evidence, both phy- 
siological and clinical, that the severe nervous dis- 
organization not infrequently follov^ing a period of 
trench v^arfare, is either directly due to a disturb- 
ance in the v^ork the glands of internal secretion, 
or at least is complicated by a glandular dyscrasia 
or dyshormonism (dyscrinism). 

The writer has had no opportunity to see cases 
of this character, but several reports from corre- 
spondents on war service have aroused an interest 
in this subject, which has lead to a study of its lit- 
erature and a comparison of this with the writer's 
personal observations. 

The excellent work of T. R. Elliott, (1) of Lon- 
don, followed by the comprehensive series of ex- 
periments by Cannon, (2) of Harvard, has quite 
definitely determined a relation between the ad- 
renal system and the sympathetic nervous system. 
It is now understood that those factors which act 
upon and through the sympathetic nervous system 



Reprinted from "The Prescriber," Edinburgh, October, 1916. 

NOTE: The editor of "The Prescriber," who is a personal 
friend of the writer, submitted certain clinical notes and sugges- 
tions, and at the same time asked for an article outlining some 
sort of a feasible explanation of the possible relation of the endo- 
crine glands to shell shock. This is merely an attempt to relate 
these. 

(62) 



IN PRACTICAL MEDICINE 63 

also influence the adrenals; and that the sympa- 
thetic manifestations resulting from pain, rage, 
fear, hunger, and the emotions cause a decided 
stimulation of the adrenals with an immediate pro- 
duction of a greatly augmented supply of adrenin 
to the circulating blood. This is followed, at a 
longer or shorter period, by an equally well defined 
adrenal depletion or hypoadrenia, accompanied by 
just such clinical manifestations as we expect to 
find in shock — vasomotor irritability and instabil- 
ity, hypotension, insomnia, depression, and an ex- 
tremely well marked asthenia. This last symptom 
is the typical accompaniment of adrenal disease 
(Addison), and almost invariably complicates the 
syndrome of pluriglandular insufficiency (hypo- 
crinism). 

This condition of hypoadrenia is not uncommon 
in consulting work, and complicates many more 
cases than one might expect. Crile's "anoci-asso- 
ciation" is nothing more nor less than an attempt 
to forestall just such a condition by the removal as 
far as possible of circumstances known to cause ad- 
renal excitation prior to operation. Sajous has long 
emphasized the importance of ''terminal hypoad- 
renia," while Sergent, of Paris, has written many 
an article upon 'Tinsuffisance surrenale." These 
contributions more than convince one that this 
endocrine syndrome is quite common. 

Judging from the foregoing physiological facts, 
''one can quite easily understand that just such a 



64 THE INTERNAL SECRETIONS 

condition would be present in individuals driven 
from home and subjected to exposure and hunger. 
Similarly, men returning from the trenches, v^here 
they have been subject to extreme fatigue and the 
tenseness of the atmosphere, as well as the mental 
effects of losing their comrades and themselves suf- 
fering from wounds and shocks, must also be con- 
sidered to be in a state of adrenal insufficiency/' (3) 
This condition of hypoadrenia was a prominent 
factor in the ''vivisection of a nation,'' so well ex- 
plained by Crile in an address delivered at the 
American Ambulance at Neuilly, during his service 
in France. (4) 

Elliot Smith, (5) of Manchester, after carefully 
considering the incidence and causation of shock in 
soldiers, intimates that mental instability is the 
most common groundwork for the superimposition 
of this condition. His position may be summed up 
in his own words: ''The real trauma is psychical, 
not physical." While it is impossible to deny that 
the impressions upon the mind are both decided 
and influential, there must also be a physical factor 
in many of these cases. 

This subject was recently referred to by Renon 
(6) in a paper read before the Societe de Thera- 
peutique, Paris, and the symptom complex which 
he describes as due to Tangoisse de guerre is almost 
typical of dyshormonism, and especially that form 
in which hypoadrenia is well marked. Renon finds 



IN PRACTICAL MEDICINE 65 

that a neuropathic or arthropathia physical sub- 
stratum is common in individuals subject to the 
more marked effects of ''war shock," and that the 
use of alcohol is a pronounced predisposing factor. 

Among the usual symptoms enumerated by 
Renon as being due to this "war neurasthenia" are 
several which can be quickly connected with the 
endocrine organs. A progressive loss of weight is 
the rule — the glands of internal secretion control 
both nutrition and growth; the temperament is 
changed and the disposition becomes uncertain — 
mental stability and activity are commonly con- 
nected with ductless glandular dyscrasias; arterial 
tension is reduced — common both in pluriglandular 
insufficiency and in hypoadrenia; dermography is 
reported to be nearly always present — one of the 
typical manifestations of severe adrenal depletion 
is the dermographic sign first mentioned by Ser- 
gent, and called by him la ligne blanche surrenale. 
I cannot but believe that the most constant single 
factor, and one that is quite susceptible to treat- 
ment, in ''shell shock" or "war neurasthenia," is 
pluriglandular insufficiency. 

That this conception of the relation of neuras- 
thenia to the internal secretions is coming to be 
more generally accepted may be noted from a re- 
cent editorial in the Journal of the American Medi- 
cal Association, (7) which comments favorably 
upon a paper by T. A. Williams, (8) of Washing- 
ton, describing the disorder as a syndrome of ad- 



66 THE INTERNAL SECRETIONS 

renal insufficiency. Williams very aptly remarks 
that the term ''neurasthenia" is only a "convenient 
cloak for failure to investigate the case sufficiently/' 
and that there must be some tangible cause. He 
concludes that many patients who show symptoms 
of neurasthenia with low blood pressure, loss of 
mental elasticity, mental and physical depression, 
and who tell of having ''lost their nerve," are very 
frequently suffering from adrenal insufficiency. He 
has given dried adrenal substance in such cases, 
and has noted improvement in many of them. 

Corbett, of Minneapolis, (9) finds that adrenin 
insufficiency is a prominent factor in shock; he 
does not maintain that its loss is shock, but rather 
that adrenin is necessary to overcome shock, and 
any factors which deplete its supply favor the de- 
velopment of that condition. Symptoms of shock 
fully develop only after the adrenals are greath^ 
exhausted, and symptoms of it become extreme the 
more marked is this adrenal depletion. He con- 
cludes that shock is a composite in which adrenin 
exhaustion and oligemia are predominant factors. 
Anesthesia, pain, fright, and trauma are immediate 
agents in producing adrenin exhaustion as well as 
shock. 

Sir James Mackenzie (10) asserts his belief that 
at least 90 per cent, of the cases of "soldier's heart" 
that have been certified and treated as cardiac aft'ec- 
tions are not primarily heart cases at all, and that 
the principles of treatment applicable in such cases 



IN PRACTICAL MEDICINE 67 

differ widely from those for the control of heart 
failure. The symptoms enumerated by Mackenzie 
are quite similar to those mentioned previously as 
being expected to follow hypocrinism and, espe- 
cially, severe adrenal exhaustion. He mentions a 
sense of fatigue or exhaustion easily induced as be- 
ing common to all — the typical ''endocrine asthe- 
nia" already noted several times. The heart's rate 
is often not increased, but in some it is persistently 
increased, as high as 120 per minute — a condition 
commonly associated with dysthyroidism. The 
mental condition is somewhat varied, periods of de- 
pression are not infrequent, and patients are often 
very irritable — both connected with dysthyroidism 
or, still more commonly, with dyscrinism. 

Mackenzie urges that the main principles of 
treatment of this heart disturbance should be de- 
voted to increasing the health of the body as a 
whole, so as to increase the natural resistance to in- 
fection, to eliminate toxic influences, and to brace 
up the whole man bodily and mentally. To achieve 
this, Mackenzie recommends fresh air and judi- 
cious exercise. While these are doubtless most im- 
portant measures, it must be remembered that re- 
sistance to infection is largely the concern of the 
thyroid gland, while the principal detoxicating 
agencies in the body are the liver, the thyroid, and 
the adrenals. In the matter of treatment, there- 
fore, it is only rational that these organs should be 
studied and, where advisable, suitablv stimulated. 



68 THE INTERNAL SECRETIONS 

From what has preceded it will appear that medi- 
cation calculated to stimulate the adrenal system 
may be helpful in cases of shell shock or neuras- 
thenia; and doubtless it is, especially if used in the 
manner suggested by Tom WilHams, i. e., desic- 
cated adrenal gland by mouth. Sergent has been 
using this form of treatment in France, (11) and 
finds it of exceptional value in the severe cases 
where the signs of acute adrenal exhaustion are 
elicited. Here hypodermic injections of adrenalin 
solution, from 15 to as high as 30 minims at suit- 
able intervals, have undoubtedly saved life. 

In the course of the discussion of Corbett's pa- 
per, (9) mentioned previously, one physician asked 
why, if these symptoms are due to adrenal insuffi- 
ciency, cannot they be relieved by the administra- 
tion of adrenalin. In his reply Corbett said he did 
not think that adrenalin, administered artificially, 
was the antidote for shock, because the amounts of 
adrenalin normally in the blood are exceedingly 
small, and if an attempt were made to maintain the 
blood pressure by forcing adrenalin, continued 
larger doses would have to be used to maintain the 
results. Such continued and increasing dosage 
would have a deleterious effect upon the blood ves- 
sels, and might increase the concentration of the 
blood, adding this factor to the shock. I am not 
sure about this effect of adrenalin on the vessels, 
but I do know that pituitary preparations are 
much more effective than adrenalin in the immedi- 



IN PRACTICAL MEDICINE 69 

ate treatment of shock and collapse, their influence 
is more prolonged, untoward by-effects, as rigors, 
coldness, palpitation, etc., are less likely to follow, 
and the general influence upon other functions, as 
diuresis, intestinal peristalsis, etc., are both salu- 
tary and desirable. Hence recourse to posterior 
pituitary preparations is now almost the rule in the 
immediate treatment of shock, though there are un- 
doubtedly cases of severe hypoadrenia, such as 
those mentioned by Sergent, Sajous, Josue and 
others, in which a dose of adrenalin might give bet- 
ter results. 

The use of one or the other of these hormone 
preparations in cases of this character is rational; 
but they are not quite suitable measures for the 
control of the chronic, unyielding, and persistent 
syndromes which outlast the actual collapse, and 
we must look elsewhere for help. 

Fortunately we have other endocrine glands 
which are so intimate with the adrenals as to be 
classified by some as a part of the "adrenal system," 
and from them we can draw in the hope of gaining 
results in this class of disorders. The thyroid, pitu- 
itary, and gonads all contain principles that are 
valuable here. Combinations of these have been 
used for some years with good results. The marked 
advantage of pituitary, for instance, over adrenal 
substance is that it contains a more stable and 
therapeutically lasting principle, and, without go- 
ing into details, its influence upon the vascular and 



70 THE INTERNAL SECRETIONS 

muscular tone seems to be much better than that 
resulting from adrenal therapy. 

The stimulating effect of small doses of thyroid 
extract is not confined to cases with obvious hypo- 
thyroidism. As a matter of fact, this influence upon 
the adrenals is well marked. Sajous, Schafer, and 
others have directed attention to the close histo- 
logical and physiological analogy which exists be- 
tween the interstitial cells of the gonads and the 
corresponding cells in the adrenals. There seems 
to be a rational as well as an empirical basis for 
pluriglandular therapy; for one is thus following 
Nature's own method by giving a mixture of sev- 
eral useful principles."^ Further than this, the vari- 
ous cell units of the body have accustomed them- 
selves to selecting those chemical messengers 
which they stand most in need of (the blood is a 
solution of unnumbered chemical substances) ; con- 
sequently, when we give several organotherapeutic 
extracts combined, the influence that may be ex- 
pected to predominate is the result of the action of 
that hormone which is most needed, and for which 
certain cells are seeking in vain, simply because the 
organ producing it has been played out. 

Another reason for giving mixed gland extracts 
lies in the fact that all these endocrine organs are 
so intimate with one another that disturbance in 
one invariably causes changes in the work of the 



*Just as we use combinations of the four food elements and 
expect the body to make use of each where it is needed most. 



IN PRACTICAL MEDICINE ' 71 

other glands upon which the first affected gland is 
dependent. According to Bayard Holmes, (12) of 
Chicago, evidence has accumulated to show that 
disease of the ductless glands is usually plural 
rather than isolated and single. "Pluriglandular 
disease is rather the rule than the exception — the 
use of gland extracts in the treatment of aplasias of 
the pluriglandular system has become an estab- 
lished therapeutic measure of miraculous potency." 

From a clinical standpoint I have had occasion to 
use a preparation called Hormotone in a number 
of cases "knocked out" by combinations of circum- 
stances other than those related to trench warfare. 
I have found it useful in various forms of neuroses 
due to toxemia or severe mental strain, and in sev- 
eral of the gynecological troubles in which there 
is a well defined dyshormonism. This preparation 
contains the so-called "dynamogenic" hormones 
from the glands which exert their principal effects 
on the adrenal system : these are the thyroid, pitu- 
itary, and gonads. Small doses of these extracts 
are useful in the adjunct treatment of just such 
cases as have been outlined in this article. I have 
had several most interesting experiences reported 
to me from Europe, and since they will form a fit- 
ting climax to this communication, a resume of 
them will be given. 

At a hospital in five cases of "trench neuras- 
thenia" were treated for some weeks with from 
2^ to 7^ grains of this preparation three times a 



72 THE INTERNAL SECRETIONS 

day, in addition, of course, to the usual expectant 
treatment. Their wounds had all healed, but the 
shock was still prominent, and tachycardia, tre- 
mors, and depression were present. All suffered 
more or less from insomnia. Two weeks of this 
treatment enabled two to be discharged '*fit for 
service," despite the fact that they had been under 
treatment ''for weeks and months with no percep- 
tible improvement." The other three grew better, 
but did not respond so rapidly. 

Another report mentions the use of this prepara- 
tion in several soldiers home from the Dardanelles 
with the usual after-effects of severe dysentery and 
nervous shock. (By the way, it has been well estab- 
lished that dysentery is a most common cause of 
hypoadrenia, while some believe that the algid 
stage of this disease, and of cholera, is essentiallv 
an acute adrenal exhaustion.) Hormotone evi- 
dently assisted in the re-establishment of the nor- 
mal ''balance," the appetite increased, and it was 
possible for these soldiers to sleep quietly and rest- 
fully. It was also remarked that they lost the feel- 
ing of depression, which, after all, is one of the 
most serious and persistent of the symptoms of 
this disorder. 

In France the practice of "opotherapie" has 
reached a much more advanced stage than in Eng- 
land or America. Pluriglandular therapy is fairly 
well established there, and there should be no rea- 
son why the results could not be duplicated any- 



IN PRACTICAL MEDICINE 73 

where. In Germany, too, this subject has not been 
overlooked, although the German literature has al- 
ways evidenced a paucity of information on organo- 
therapy, most of the real advances in this line hav- 
ing emanated from other countries. Thyroid was 
introduced by George Murray, of Manchester; 
pituitary medication b}' Blair Bell, of Liverpool; 
parathyroid treatment by Vassale, of Turin, and 
Berkeley, of New York; adrenalin, as all know, 
originated in the investigations of Aldrich and 
Takamine; the corpus luteum was first studied in 
France; Brown-Sequard, of Paris, is the "father of 
scientific organo-therapy" ; hepatic opotherapy was 
first used by Gilbert and Carnot, of Paris, etc. The 
only reference to this subject in recent German lit- 
erature is that of Kohnstamm, (13) who relates a 
number of instances in which thyroid, hypophysis, 
or adrenal preparations were used to improve the 
morbid conditions resulting from disturbances in 
the internal secretions caused by the emotional 
strain of the soldier's life while on active service. 

I believe that the systematic administration of 
pluriglandular extracts opens up a new era in or- 
ganotherapy. As an adjunct to other indicated 
treatment it favors the restoration of the disturbed 
"hormone balance," so well discussed by Harry 
Campbell, (14) and others. The theoretical side of 
this subject is outlined quite fully in my book, (15) 
and since its publication I have had many oppor- 
tunities to test its efficacy in civil practice. I be- 



74 THE INTERNAL SECRETIONS 

lieve that it will be just as efficacious in the treat- 
ment of soldiers, and that the results already se- 
cured are a pleasant foretaste of what may be ex- 
pected by applying this suggestion much more ex- 
tensively. 



Since the above was published it has come to my 
attention that the application of pluriglandular 
therapy in similar conditions both in this country 
and abroad is indeed an efficacious measure, even 
though the foregoing explanation may not be be- 
yond discussion. One case in particular comes to 
mind: A man, previously in good health, went 
through a ''near accident" but was not hurt. His 
blood pressure was 80 mm., his temperature was 
subnormal, his heart action hurried and he was ob- 
viously suffering from shock. Tonic organother- 
apy ''acted like a charm" and by the thermometer, 
sphygmomanometer and stethoscope it seemed 
quite clear that a very tangible service had been 
rendered. 

Another case of a somewhat similar nature was 
recently reported by Dr. Vanderwyst of Kansas. A 
girl of 17 had manifested a neurosis for five years 
following a severe experience with a cyclone when 
she was twelve years old. Since then her tempera- 
ture has been very unstable, she suffered from vari- 
ous vasomotor disturbances and was subject to se- 
vere emotional "storms." She was much run down, 
anemic and suffered from transitory attacks of pain 



IN PRACTICAL MEDICINE 75 

in different parts of the body, especially in th^. 
spine. 

After varied and protracted treatment she was 
given a course of pluriglandular therapy repre- 
sented by the Roberts-Hav^ley Lymph with a very 
remarkable re-establishment of normal emotional 
and nervous stability as well as an accompanying 
gain in weight and health. 

This is but an additional indication, to the writer 
at least, that the dynamic or antiasthenic effect of 
hormone therapy is deserving of consideration in 
the neurasthenic manifestations due to or akin to 
"shell shock." 

REFERENCES 

1. Elliott: Jour. Physiol., 1905, xxix, 363; 1912, xliv, 
374. 

2. Cannon, et al. : Amer. Jour. Physiol., 1911, xxviii, 
64; 1911, xxix, 274; 1914, xxxiii, 356. 

3. Editorial: Amer. Med., 1915, xxi, 590. 

4. Crile: Surg. Gyn. and Obs., 1915, xvii, 708. 

5. Smith : Lancet, 1916, cxc, 813. 

6. Renon: Jour, des Practiciens, Jan. 15, 1915. 

7. Editorial : Jour. Amer. Med. Assoc, 1915, Ixv, 2166. 

8. Williams : Jour. Amer. Med. Assoc, 1914, Ixiii, 2203. 

9. Corbett: Jour. Amer. Med. Assoc, 1915, Ixv, 380. 

10. Mackenzie: British Med. Jour., 1916, i, 117. 

11. Sergent: Bull. Acad. Med. Paris, Sept. 7, 1915; 
see Amer. Med., 1915, xxi, 922. 

12. Holmes : Lancet-Clinic, 1914, cxiii, 705. 

13. Kohnstamm : quoted in Critic and Guide, 1916, 
xix, 153. 

14. Campbell: Lancet, 1907, i, 313 et seq. 

15. Harrower: "Practical Hormone Therapy," Bal- 
liere, 1914. 



VII 

THE ADRENAL GLANDS AND THEIR SIG- 
NIFICANCE IN GENERAL PRACTICE 

THE study of the adrenal glands has received a 
great impetus since Cannon recently announced 
his epoch-making discoveries of the physiological 
changes in these glands dependent upon the emo- 
tions. The practical application of this new knowl- 
edge is important, though it is not yet appreciated 
as much as it deserves. Sometimes it takes a long 
time for the experiences of the physiologists in 
their laboratories to be translated into terms of 
every-day utilit}^ to the practicing physician; and 
in my somewhat broad association with physicians 
in different parts of the world, during which we 
have almost invariably discussed matters pertain- 
ing to the internal secretions, I have noticed quite 
a lack of appreciation of the clinical value of Can- 
non's work. 

Briefly, we now know that the emotions, fear, 
rage and pain, stimulate the adrenal glands ; and it 
is believed that many of the phenomena which usu- 
ally accompapny emotional strain, really result 
from the excessive amount of adrenin liberated 
from the adrenal medulla by the psychic stimuli; or 
from the glandular depletion which one would nat- 



Read by invitation before the Pasadena branch of the Los 
Angeles County Medical Association, and published in the Medi- 
cal Review of Reviews (New York) May, 1917. 

(76) 



IN PRACTICAL MEDICINE 77 

urally expect to follow excessive functional activ- 
ity. 

I am confident that if this fundamental physio- 
logical principle v^ere kept in mind, and the connec- 
tion betv^^een the adrenals and certain affections 
was understood, the appreciation of this usually 
overlooked element would make a good deal of dif- 
ference to the diagnostics and the therapeutics of 
these conditions — would further revolutionize our 
conceptions of disease. It is for these reasons that 
I have chosen this subject for brief consideration 
to-night, and I am confident that much practical 
good can come from the clinical application of Can- 
non's remarkable experiments. To those who may 
become interested in the intricacies of this matter 
I warmly recommend Cannon's book, "Bodily 
Changes in Pain, Hunger, Fear and Rage,"* in 
which the subject is considered from its experi- 
mental aspect. It is a fascinating book. 

With these new principles in mind we can now 
begin to explain the sudden onset of serious symp- 
toms and even diseases, following some severe 
mental shock. We can understand more thor- 
oughly the comparatively recently discussed kinetic 
system, as well as what Crile pleases to call "anoci- 
association," both of which are intimately related 
with the function of the adrenal glands, especially 
as it is influenced by pain, mental stimuli and the 



D. Appleton & Company, New York, 1915. $2.00. 



78 THE INTERNAL SECRETIONS 

emotions. There is a much wider application of 
this than that which is being so successfully applied 
by Crile and his followers in their surgical work. 

Let us first recall the physiological reactions 
which result from excessive or deficient adrenemia. 
An increased output of the chromaffin hormone, 
adrenin, favors the production of an increased sym- 
pathetico-tonus, increases the reactivity of the or- 
ganism to all sorts of impressions, augments car- 
diac action, raises the arterial tension, hinders in- 
testinal motility and causes a decrease in the func- 
tions of the pancreas, especially as regards its in- 
ternal secretory capacity with possible glycosuria 
(clinically analogous to the experimental ''adren- 
alin glycosuria" following injections of this sub- 
stance, as well as to the "experimental pancreatic 
diabetes" which invariably follows removal of the 
islets of Langerhans). 

On the other hand the chromaffin cells may be 
so unduly stimulated that they become transiently, 
or even permanently, played out ; and a condition of 
adrenal insufficiency ensues, which is quite com- 
mon in general practice as we will shortly see. This 
hypoadrenia is responsible for reduced sympathetic 
tone, lessened muscular excitability and capacity 
with exhaustion on slight exertion, or asthenia 
(quite the most prominent and constant symptom 
of this disturbance), reduced cardiac power and, 
sometimes, rate, lessened blood pressure and. 
finally, collapse or shock with pallor, clammy, cold 



IN PRACTICAL MEDICINE 79 

skin, dilated pupils and respiratory excitement and, 
later, failure. 

To my mind it is quite proper to consider a pos- 
sible adrenal cause for each symptom just enumer- 
ated. Very often it may be the chief cause and, 
too, other causes which also may be present are in 
part due to the adrenal factor. 

Perhaps we might recapitulate just what Cannon 
demonstrated. He showed that the emotion of fear 
suffices to cause an increased stimulation of the 
flow of the adrenal secretion, and blood taken from 
the adrenal veins of frightened animals is so rich 
in adrenin as to be able to inhibit the peristaltic 
contraction of isolated strips of intestinal muscle 
which were immersed in the blood. This also has 
been shown to result from the presence, in appre- 
ciable amount, of adrenalin since contact with this 
commercial chemical substance in a dilution as in- 
significant as 1 :1, 000,000 will bring about the same 
experimental results upon isolated intestine. 

Some day a comparatively easy technic will be 
evolved for the clinical measurement of adrenal 
activity. Many a time I have wished that I might 
be able to determine the degree of adrenal function- 
ing in a given case. For example, some individuals 
are more susceptible to external impressions than 
others, and of these there are some who suffer 
much longer as a result of serious excitement than 
others; they ''take a long time to get over" such 
experiences. If, now, we were able to estimate 



80 THE INTERNAL SECRETIONS 

with some degree of comparison the adrenin con- 
tent of the blood of these persons, we would be able 
to know whether the adrenal element was promi- 
nent, could measure the degree of its depletion or 
excitation, and, naturally, would be better able to 
control the deviations from the average. 

On the other hand, in cases suffering from the 
after effects of this excessive stimulation, as in 
shock, collapse or severe asthenia, we might be able 
to estimate in actual figures the factor of restora- 
tion and see how well and how rapidly the depleted 
adrenals were unable to functionate. In other 
words, we would be able to measure hyper- or hypo- 
adrenia. 

A means of accomplishing this has been sug- 
gested by Ehrmann, and is sometimes called '^thc 
frog's eye test." It consists of immersing a re- 
cently enucleated frog's eye into the blood serum 
of the patient under examination. One notes the 
time elapsing from the moment that the eye is im- 
mersed in the serum, until the pupil reaches maxi- 
mum dilatation. This may be compared with a 
scale previously made by performing the same ex- 
periment with definite solutions of adrenalin. It is 
thus possible to estimate comparatively the amount 
of adrenin present in the blood serum examined, 
though this method is somewhat crude and by no 
means accurate, for we do not know with certainty 
that the mydriasis is of purely hormonic origin. 
Also adrenin and adrenalin are very easily oxidiz- 



IN PRACTICAL MEDICINE 81 

able substances, and this militates against an alto- 
gether dependable test. There is no doubt, how- 
ever, that some day we will have a clinical diag- 
nostic procedure for the determination of the ex- 
tent of the adrenal activities. I have suggested 
that some sort of a colorimetric test should be pos- 
sible, and before long I believe that some chemist 
or physician is going to work it out. 

The interrelation of the endocrine glands is so 
complex and intimate that it is practically impos- 
sible to have a marked deviation from the func- 
tional normal of one gland without a correspond- 
ing increase or decrease in the work of the others. 
This is the basis of the complexities of endocrinol- 
ogy and the reason for the numerous reports of 
pluriglandular disorder we are beginning to find in 
the literature. Parenthetically, it is often also the 
reason for failures in the treatment of this class of 
cases, for a presumed thyroid disorder is treated as 
a thyroid disorder pure and simple, when further 
investigation would couple one or more glands 
with it — often the pituitary, gonads or adrenals — 
and the treatment modified by this broader view 
would be much more effectual. 

So adrenal stimulation by emotional causes, by 
toxemia or by changes in the hormone balance, 
may cause other ductless glandular disorders. For 
instance, fright often has much to do with the 
onset of hyperthyroidism. I have seen a severe 
shock cause exophthalmic goiter over night. Crotti 



82 THE INTERNAL SECRETIONS 

mentions the case of a man of 42 who had Graves' 
disease which developed in a few hours at the time 
of the San Francisco earthquake. I commonly find 
indications of this relationship in my consultation 
work, and there are numerous reports in the litera- 
ture to substantiate this. In such cases I am con- 
vinced that the etiologic influence is not so much 
nervous as hormonic; and I explain this to myself 
by presuming that the undue stimulation of the ad- 
renals by emotional strain causes a severe increase 
in their secretory activities which, so to speak, 
gives a very strong push to the thyroid pendulum, 
causing it to swing much more rapidly and in a 
longer arc. 

While we are speaking of hyperthyroidism, I 
would like to remark that anger, fear and, espe- 
cially, worry are factors which play a very im- 
portant part in the treatment of all forms of this 
disorder. I have a case at present in whom the 
symptoms are always aggravated by concern over 
home matters, and the best of treatment, with ab- 
solute rest in hospital or out, is largely overbal- 
anced by the fears and worries so difficult to con- 
trol. A part of the proper treatment of hyperthy- 
roidism is not merely rest, but absolute quiet away 
from the "hospital noises" and the removal of all 
things likely to disturb the emotional balance; in 
other words the prevention of adrenal stimulation 
just as Crile prevents this same thing in his surgi- 
cal work by his methods of pan-anesthesia. The 



IN PRACTICAL MEDICINE 83 

administration of adrenalin, or the equally useful 
adrenal substance, may in some cases offset severe 
adrenal depletion. 

Undoubtedly adrenal dysfunction is capable of 
causing digestive disorders. Crile has shown ex- 
perimentally that among the functions of the ad- 
renals is the power to inhibit intestinal function 
provided the adrenals are working to excess. Can- 
non confirms this, and has proved that a forced out- 
put of adrenin produces an increase in the arterial 
tension by shifting the blood from the compara- 
tively less important abdominal viscera to the im- 
mediately essential organs as the brain, lungs and 
heart. It seems that there is enough clinical proof 
to implicate the adrenals in epilepsy. Adrenal ex- 
cess tends to increase circulatory stasis in the brain, 
inhibits both pancreatic digestion and intestinal 
muscular activity and thus favors toxemia; factors 
which unquestionably are prominent in the syn- 
drome of epilepsy. We all know that fright may 
be a part of the original cause of epilepsy, and also 
that a sudden shock or grief may badly upset the 
digestion. 

Some interesting comments on the relation of 
the adrenals to intestinal stasis and epilepsy are to 
be found in a recent paper coming from the New 
Jersey State Hospital. Cotton and his associates 
there conclude that at least one type of epilepsy is 
probably a disease process dependent upon the ab- 
sorption of toxic products from the intestinal canal. 



84 THE INTERNAL SECRETIONS 

This stasis may be produced by an overaction of 
the adrenal glands which, in turn, may be caused 
by dysfunction of the pituitary body or the pan- 
creas, irritation of the duodenum, or severe fright 
or emotional disturbance. They then suggest that 
the administration of pancreatin should be em- 
ployed in preference to surgical measures in the 
treatment of epilepsy. Incidentally this form of 
organotherapy is physiologically opposed to the 
action of the adrenals; it favors digestion, and it 
has been remarked that the pituitary is also an 
antagonist of the pancreas. At least Cotton's 25 
or 30 cases encouraged him to make the above de 
ductions and to report his good results with pan- 
creatic organotherapy in epilepsy. I mention this 
for what it is worth; at least it amplifies my opinion 
regarding the importance of the adrenals in this 
disease. Note especially that toxemia causes hyper- 
adrenia; that hyperadrenia causes toxemia (a vi- 
cious circle) and intestinal insufficiency, factors in- 
volved in many another syndrome besides epilepsy, 
Pottenger has been doing some very interesting 
work involving the adrenal glands with some of the 
findings in certain forms of pulmonary tubercu- 
losis. He has shown quite recently that the con- 
tinued stimulation of the adrenals, presumably by 
the toxins of this disease, and the continued pour- 
ing into the blood of even minutely increased 
amounts of adrenin, brings about conditions re- 
sulting from sympathetic stimulation, including 



IN PRACTICAL MEDICINE 85 

the very dry mouth not uncommonly seen in tuber- 
culosis, as well as other clinical findings, as the 
rapid heart action and the sudden and quite serious 
disturbances of digestion that one meets from time 
to time in tuberculosis. 

I have put forward a theory regarding the ad- 
renals in malaria which is yet to be discredited or 
proved. I believe that at one stage in the cycle of 
experiences in malaria there is a decided adrenal 
excitation, due to the sudden periodical liberation 
of the Plasmodia and, of course, their toxins. One 
encounters the dry mouth as often as salivation, 
both manifestations of sympathetic stimulation. 
The heart action is always rapid and sometimes ir- 
regular. Then, as an aftermath of the chill, we find 
the muscular relaxation, prostration, depression 
and asthenia, all of which are identical with the 
findings of severe adrenal insufficiency. 

If this idea is reasonable it should apply with 
equal force in other toxic infectious diseases and 
acute toxemias, such as typhoid fever and pneu- 
monia; and Josue, Sergent and other French writ- 
ers have accumulated undeniable evidence to show- 
that the ultimate outcome of acute infectious dis- 
ease includes a very severe adrenal depletion which 
not uncommonly may be the actual cause of death. 

The most frequent form of serious adrenal dis- 
order, then, is not Addison's disease, but what 
Sajous has called "terminal hypoadrenia." This is 
the frequently fatal ending of septicemia and all 



86 THE INTERNAL SECRETIONS 

serious toxemias as diphtheria, cholera and the like. 
In fact the algid stage of cholera, like the fatal 
"turn for the worse" in erysipelas or pneumonia, is 
brought on when the severe bacterial poisoning 
and accompanying cellular depletion causes acute 
hypoadrenia with collapse, heart weakness, a drop 
in the temperature and death. In such desperate 
stages the tide has been turned by intravenous in- 
jections of adrenaUn, as much as 30 min. of the 
1 :1000 solution having been given with a happy 
outcome. This fundamental principle is worth re- 
membering in such extremes, for the logical treat- 
ment is occasionally amazingly resurrective. 

In gynecological practice the adrenal glands may 
play an important role. I shall shortly direct your 
attention to their relationship to neurasthenia, and 
here wish you to recall the frequency with which 
severe asthenia accompanies ovarian disease. To 
illustrate, I recently saw a case in Omaha of ex- 
treme asthenia. This came on pepriodically in con- 
nection with the menses, and during the month 
there were, perhaps, five or six days in which the 
extreme lassitude and inability to accomplish any- 
thing were slightly modified. The weakness was 
absolute and had continued for years. The diag- 
nosis was hypoadrenia superinduced by dysovarian 
or ovarian toxemia. In this case surgery gave 
some benefit, I believe, for a diseased ovary was 
removed in my presence and a cyst in the other 
was also removed. From the standpoint of this 



IN PRACTICAL MEDICINE 87 

paper the case was of special interest, for the myas- 
thenia as well as the neurasthenia was undoubtedly 
due to the abnormal stimulation of the chromaffin 
cells by this poisonous ovarian hormone, and the 
patient was thus in a practically perpetual state of 
hypoadrenia. 

I do not wish to commit myself to-night, but I 
have studied a number of cases of functional dys- 
menorrhea from the standpoint of endocrinology, 
and I must confess that I have strong suspicions 
that many of the symptoms, especially those of a 
sympathetic nature, are of adrenal origin; and if 
so the trouble is probably brought about by this re- 
flex (hormonic) stimulation of the adrenals by the 
ovaries. 

There is much reason to believe that adrenal dys- 
function is a factor which deserves a good deal 
more responsibility placed upon it for the causation 
of neurasthenia than as yet has been given to it. 
In a recent article in my series, "The Diagnosis of 
the Internal Secretory Disorders" (Western Medi- 
cal Times, Sept., 1916) you will find an outline of 
some facts connecting the adrenals with neuras- 
thenia. I will quote a few paragraphs here: 

''Minor functional hypoadrenia is more common 
than some have appreciated, and the fact that there 
is a psychic origin as well as other physiologic 
causes already considered, allies it to the fashion- 
able 'neurasthenia* of to-day. In fact some have 
stated that what is improperly called 'neurasthenia' 



88 THE INTERNAL SECRETIONS 

is not a disease per se, but really a symptom com- 
plex of ductless glandular origin, and that the ad- 
renals are probably the most important factors in 
its causation. Campbell Smith, O. T. Osborne, 
Tom Williams and others, including the writer, 
have directed the attention of the profession to the 
importance of the adrenal origin of neurasthenia 
(though a pluriglandular dyscrasia is practically 
always discoverable), but so far this is not under- 
stood as well as its frequency and importance war- 
rant. 

"The subject is too large to receive exhaustive 
consideration here, but a few quotations from re- 
cent literature will firmly establish the importance 
of this angle from which to study this common and 
annoying symptom complex. Quoting first from 
the Journal of the American Medical Association 
(Dec. 18, 1915, p. 2166) : 'The typical neurotic gen- 
erally has, if not always, disturbance of the thyroid 
gland. The typical neurasthenic probably gener- 
ally has disturbance of the suprarenal glands on 
the side of insufficiency. The blood pressure in 
these neurasthenic patients is almost always low 
for the individuals, and their circulation is poor. A 
vasomotor paralysis, often present, allows chill- 
ings, flushings, cold or burning hands and feet, 
drowsiness when the patient is up, wakefulness on 
lying down and hence insomnia. There may be 
more or less tingling or numbness of the extremi- 
ties.' 



IN PRACTICAL MEDICINE 89 

"Again Kinnie Wilson, of London, in his mono- 
graph on 'The Chnical Importance of the Sympa- 
thetic Nervous System' makes the following perti- 
nent remarks: 'Many of the common symptoms 
of neurasthenia and hysteria are patently of sympa- 
thetic origin. Who of us has not seen the typical 
irregular blotches appear on the skin of the neck 
and face as the neurasthenic subject ''works him- 
self up into a state"? The clammy hand, flushed 
or palHd features, dilated pupils, the innumerable 
paresthesias, the unw^onted sensations in head or 
body, are surely of sympathetic parentage. In not 
a few cases of neurasthenia symptoms of this class 
are the chief or only manifestations of the disease. 
Here, then, is a condition of defective sympathet- 
ico-tonus ; may it not have much to do with im- 
pairment of function of the chromophil system? 
. . . There does not appear to be any tenable dis- 
tinction between the asthenia of Addison's disease 
and the asthenia of neurasthenia. Cases of the for- 
mer are not infrequently diagnosed as ordinary 
neurasthenia at first. It is difficult to avoid the con- 
clusion that defect of glandular function is respons- 
ible for much of the clinical picture of neuras- 
thenia.' " 

Be prepared to look for the adrenal element in 
gynecology or in neurasthenia and it will surprise 
you how common it really is. Kinnie Wilson, in 
the same address from which the above quotation 
was made, also made the following apothegm: 



90 THE INTERNAL SECRETIONS 

"Sympathetic tone is dependent on adrenal sup- 
port, and until the glandular equilibrium is once 
more attained, sympathetic symptoms are likely to 
occur." 

In closing I might point out that these reactions 
resulting from adrenal excess possibly may explain 
the occasional effects of psychanalysis, suggestion 
and even Christian Science in certain neurotic or, 
more properly, sympathetico-tonic states. One can 
readily see that a calmed mind — reduced emotional 
overstrain — obviates the excessive psychic stimula- 
tion of the adrenals; and the hypertonic state of 
hyperadrenia or the later asthenic state of hypo- 
adrenia are thereby allov^ed to right themselves by 
Nature. 

This may be visionary, but I still insist that we 
are going to connect the adrenal glands with nu- 
merous conditions encountered in general practice, 
particularly those connected with the emotions, 
more and more as we come to understand their 
functions and interrelations better. 



VIII 

THE ASTHENIAS: 
NEURASTHENIA, PSYCHASTHENIA, MY- 
ASTHENIA AND CHEMASTHENIA— 
ENDOCRINASTHENIA 

OF ALL the difficulties encountered in general 
practice the asthenias constitute quite a large per- 
centage. Naturally neurasthenia occupies a promi- 
nent place, but this is by no means the only asthe- 
nia which we have to meet. It is the opinion of the 
writer that endocrinasthenia is a very much more 
important condition than yet appears. In fact this 
word is not yet found in our most recent diction- 
aries and while there is plenty of literature upon 
ductless glandular insufficiencies, so far as I know 
the subject has not been extensively considered 
from this angle. 

The hormones, or the "regulators of metabo- 
lism" as Noel Paton has called them, bring about 
a series of chemical reactions which really must be 
considered as sthenic in character. The word "hor- 
mone" comes from the Greek, "I arouse," and it is 
not a very great stretch of imagination to consider 
asthenia as representing "I lie down." 

There is an accumulating weight of evidence in 
clinical practice which is being reflected in current 
literature which indicates that many forms of as- 
thenia properly may be called of endocrine origin 

(91) 



92 THE INTERNAL SECRETIONS 

or endocrinasthenia. The arousing stimuli are les- 
sened or lost. The body, or a part of it as the case 
may be, is tired out, function has been disorganized 
by numerous factors and the resulting loss of 
strength and activity may affect the muscles, 
nerves, mentality, metabolism or, for that matter, 
any other bodily function. It seems quite reason- 
able to believe that if the endocrine glands are af- 
fected by conditions which' render them inactive, 
the natural outcome v^ould be a condition of gen- 
eral functional somnolence, or as we call it ''asthe- 
nia"; while any attempt to bring about greater 
activity on the part of the glands of internal secre- 
tion must necessarily arouse the metabolic func- 
tions in general as well as certain of the results of 
this hormonic function in particular. 

If this is the case, we must revise our consid- 
eration of the origin as well as the treatment of all 
forms of asthenia and from a practical standpoint 
this seems to be a profitable advance in medicine, 
for w^hen we treat the various asthenias with the 
internal secretory factor prominently in our minds, 
the results really seem to be better and more per- 
manent than though we merely prescribe rest and 
a hygienic regimen calculated to reduce the tox- 
emia. 

Of course rest is most advantageous in the treat- 
ment of all forms of fatigue whether natural or 
pathologic, though many individuals suffer from 
forms of tiredness which are not remedied bv in- 



IN PRACTICAL MEDICINE 93 

activity and sleep — they are the ones who ''get up 
tired." Preventive measures usually do not suffice 
to secure tangible results in cases of this charac- 
ter, and treatment calculated to remove as many of 
the obvious conditions favoring the asthenia is very 
much more satisfactory in its results if efforts are 
made simultaneously to re-establish the normal hor- 
mone producing functions. 

With these preliminary considerations in mind 
we will consider briefly the various asthenic states 
and attempt to connect them with one or more of 
the glands of internal secretion and, having done 
so, it must be left to the reader to apply his own 
deductions and modify his treatment of asthenic 
states accordingly. 

To those who take time to study endocrinology 
in its relation to the practical side of medicine, it 
becomes quickly apparent that the most important 
functions of the glands of internal secretion are of 
an aggressive or stimulating nature, and further, 
that the most common endocrine disorders are in 
the nature of an insufficiency. With all such insuffi- 
ciencies, whether they be thyroid, pituitary, adrenal 
or gonad in origin, asthenia is an almost invariable 
accompaniment. The chief diagnostic or clinical 
necessity then, would appear to be the appreciation 
of early forms of endocrine insufficiency or hypo- 
crinism and, where possible, the differentiation or 
evaluation of functional insufficiency of the glands 
that are affected. 



94 THE INTERNAL SECRETIONS 

The thyroid gland is responsible for a very large 
measure of the metabolic activities of the body and 
is susceptible to the subtle influences of numerous 
very common disorders, for toxemia of all kinds 
affects the thyroid as early as any other part of 
the body and infections, whether general or focal, 
not infrequently disturb the normal functioning of 
this gland. The French have called the thyroid 
''the emotional gland" since it is intimately related 
to the emotions, but we now believe that much of 
this supposed connection is not direct, but is 
brought about through the intimacy of the adrenals 
with the thyroid. Theoretically these conditions 
should stimulate the thyroid and it is perfectly true 
that many cases of thyroid excess are the result 
of just such stimuli, but it is none the less a clinical 
fact that insufficiencies are more frequent than the 
opposite conditions and hypothyroidism, especially 
the minor form, is very much more common than 
hyperthyroidism. 

The cHnical importance of the minor forms of 
thyroid insufficiency has been fully discussed else- 
where* and if the study of individuals suffering 
from any form of asthenia is made to include a 
search for definite indications which would lead 
one to incriminate the thyroid gland, treatment cal- 
culated to stimulate this gland is very likely to 
make a favorable impression upon the course of the 



*See Chapter IV. 



IN PRACTICAL MEDICINE 95 

disorder.f If one reads much of the literature on 
thyroid disorders and even limits it to the writings 
of Eugene Hertoghe, Leopold Levi, George Mur- 
ray or Gabriel Gauthier he v^ill be quickly con- 
vinced of the extreme frequency of asthenia as a 
manifestation of all forms of subthyroidism from 
the most insignificant and easily overlooked to the 
best clinically defined or text-book varieties. 

Our knowledge of the adrenal glands is inex- 
tricably connected with asthenia for the most 
prominent of all the symptoms described in 1855 
by Addison, is asthenia of a most marked type. Of 
course Addison's disease is an organic adrenal dis- 
order and it is not necessary for an individual to be 
suffering from this incurable disorder in order to 
have the symptoms of functional adrenal insuffi- 
ciency. As a matter of fact this latter disorder is 
almost as common as the minor functional thyroid 
troubles to which attention has just been drawn, 
and as we now believe that the adrenals are de- 
pleted as a result of the stimuli of emotion, tox- 
emia, pain or certain disorders of other glands of 
internal secretion, we can readily see how easy it is 
to incriminate these glands in the asthenias as a 
class. The clinical findings in severe hypoadrenia, 
quite different from the Addison syndrome, always 
include asthenia as a most prominent condition, for 
what is shock or collapse if it is not an extreme 



♦This treatment, by the way, may be numbered among the 
few "specifics" which we have in medicine. 



96 THE INTERNAL SECRETIONS 

manifestation of vasomotor as well as muscular as- 
thenia? 

The pituitary gland, too, exerts what properly 
might be called a sthenic effect. Its influence alone 
is not quite so marked as that of the adrenals or 
the thyroid, but we know that the posterior lobe 
at least contains markedly stimulating substances 
and it should not be improper to presume that de- 
ficiencies in the production of this and other simi- 
lar substances in either lobe of the gland must exert 
some opposite effect upon the organism. In fact 
recent German writers have definitely connected 
certain forms of cachexia with pituitary insuffi- 
ciency and seemingly have established their con- 
tention by modifying these conditions with pitu- 
itary feeding. 

We also know that pituitary insufficiency is 
sometimes responsible for a syndrome described by 
Froehlich and Bartels in which metabolic insuffi- 
ciency (chemasthenia) is present as well as a defi- 
ciency in the production of the so-called dynamo- 
genie hormones with a resulting infantilism or 
asexuality. I recall a very interesting case of asex- 
uaHty unaccompanied by any findings which would 
warrant the diagnosis of the Froehlich syndrome, 
in which a radiographic examination of the sella 
turcica showed a very decided diminution in size 
of the pituitary body. Additional evidence from 
the opposite side is now discoverable in the litera- 
ture and I have had some favorable clinical experi- 



IN PRACTICAL MEDICINE 97 

ences myself with the administration of pituitary 
substance in functional impotence. 

Tom Williams of Washington, in a most inter- 
esting discussion of the endocrine neurasthenias 
(Medical Record, April 14, 1917), tells of an ob- 
scure condition in a business man which was de- 
scribed as "a general feeling of discomfort, some- 
times with intense fatigue'' which was traced event- 
ually to a disorder of the pituitary gland. 

Without a doubt the pituitary must be consid- 
ered as a possible factor in the production of many 
of the asthenic manifestations and while the Ab- 
derhalden test as amplified and made practical in 
the Corson-White laboratory in Philadelphia, is 
often helpful, it is not so difficult to secure a sellar 
radiograph in suspected cases. 

The thymus gland is perhaps the least appreci- 
ated and understood of the glands of internal secre- 
tion. Its persistence in the adult is often accom- 
panied by a severe asthenia, especially myasthenia, 
and thanks to the work and writings of G. H. 
Hoxie of Kansas City, we are beginning to under- 
stand more about this clinical relationship. It 
should not be amiss in the study of a well defined 
asthenia which resists treatment, to establish or 
rule out by careful physical diagnostic measures 
and the X-ray the possible presence of a persistent 
thymus. 

Still another gland recently has been associated 
with myasthenia. Timme (Archives of Internal 



98 THE INTERNAL SECRETIONS 

Medicine, Jan., 1917) has intimated that that in- 
tractable neuro-trophic disease, myasthenia gravis, 
may be quite likely of endocrine origin and the 
epiphysis or pineal gland a possible source of its 
cause. This has not been proven, but it may be 
that once again an enigma heretofore unsolved will 
be made clear by a broader knowledge of endocrin- 
ology. 

The sex glands are unquestionably the drivers of 
the organism. It is not necessary to dilate upon 
the relation of their activities to muscular, mental 
or metabolic function. There is much clinical evi- 
dence to establish this position and the renowned 
experience of Brown-Sequard who injected testicle 
juice into himself and discovered an immediate en- 
hancement of his physical powers and endurance 
as well as a diminution in the asthenia due to his 
age, was really the beginning of scientific organo- 
therapy, and times without number since 1889 the 
hormonic importance of the gonads has been estab- 
lished experimentally and clinically, as well as 
therapeutically. 

The natural corollary of the discovery of a gland- 
ular insufficiency is an attempt to re-establish it, 
and the most satisfactory and scientific manner to 
accomplish this is by recourse to judicious organo- 
therapy. It is true that these insufficiencies rarely 
are seen singly and that ductless glandular dis- 
orders invariably affect several or all of these or- 
gans, hence while this complicates our diagnostics 



IN PRACTICAL MEDICINE 99 

and favors a tendency to empiricism, none the less 
we cannot permit ourselves to ignore endocrine de- 
ficiencies just because v^e may not be able to label 
them accurately or to measure the comparative de- 
ficiencies of this gland or that. Without a doubt 
the "unscientific" administration of mixed glandu- 
lar extracts whether proprietary as "hormotone" 
or otherwise (as, for example, the ''Tabloid mixed 
glands" suggested by E. B. McCready of Pitts- 
burgh) has remedied materially many hundreds of 
cases, and it is my custom when attempting to 
treat an asthenia, whether neurasthenia, myasthe- 
nia, psychasthenia or chemasthenia, to consider it 
always as a manifestation of endocrinasthenia and 
to supplement the hygienic and other allied meas- 
ures with the indicated glandular feeding or, in 
suitable cases, with the hypodermic administration 
of the so-called Roberts-Hawley lymph combina- 
tion of which, unfortunately, there is still too little 
said in current medical literature. 



IX 

THE RELATION OF THE INTERNAL SE- 
CRETIONS TO NEURASTHENIA 
IN WOMEN 

"THE condition called 'neurasthenia' — a symp- 
tom-complex rather than a distinct disease — is be- 
ing more carefully studied these days. Our knowl- 
edge, however, still seems to be just as indefinite 
to-day as it has always appeared to be, for the opin- 
ions regarding neurasthenia have differed even 
more than the ideas of all medical men usually dif- 
fer. It would appear that the organs of internal 
secretion are to be charged with causing many of 
the disorders which together form the neurasthenic 
syndrome. In fact the more we study the neuras- 
thenic individual and observe closely the incidental 
variations in functional activity, the more evident 
it becomes that neurasthenia rarely exists without 
some associated disturbance in the work of the 
ductless glands." 

The foregoing quotation from an editorial in 
American Medicine (August, 1915, p. 590) is a fit 
introduction to the subject that has been chosen 
for consideration this evening. As our knowledge 
of these glands of internal secretion becomes more 
extensive and connected, one can appreciate more 



An address read before the Los Angeles Obstetrical Society, 
December 14, 1915, and reprinted from the American Journal of 
Obstetrics and Diseases of Women and Children, April, 1916. 

(100) 



IN PRACTICAL MEDICINE 101 

thoroughly how intimate is their association with 
one another, as w^ell as with the etiology of many 
functional disorders and even, occasionally, an or- 
ganic disease. In no phase of endocrinology do we 
see that intricacy of these relationships more defi- 
nitely, than in the numerous functional disorders, 
the treatment of which constitutes the largest part 
of the work of the gynecologist. 

From the time that the thymus begins to retro- 
grade and its antagonism to the functional activity 
of the gonads is gradually reduced, there is an in- 
crease in the physiologic activities of the thyroid 
and the ovaries, as well as in most of the other 
ductless glands which are built in with these key- 
stones of the endocrine arch. It is an everyday oc- 
currence to see thyroid enlargement at puberty, 
and it is now well known that the essential sex 
manifestations as well as the organic changes 
which accompany them, are due to the production 
of a series of chemical messengers and the main- 
tenance between them in the fluids of the body of 
what has come to be known as the ''hormone bal- 
ance." 

Disturbances of this balance are responsible for 
most of the functional disorders in women. This 
is a broad statement, I know, and it will be ques- 
tioned by some who still are certain that the nerv- 
ous system and derangements of it, are responsible 
for many functional gynecological disturbances. 
However, it has been stated by more than one in- 



i02 THE INTERNAL SECRETIONS 

vestigator of authority that the nervous system it- 
self, and more especially the sympathetic nervous 
system, is under the direct control of certain of the 
endocrine organs; and the conclusions made by 
Cannon, of Harvard, as to the relation of the emo- 
tions to adrenal activity, indicate that the adrenal 
medulla is a prominent factor in the causation of 
many manifestations commonly associated with 
fear, rage or pain. Now the chromaffin tissue of 
the adrenal medulla is but an integral part of the 
endocrine system, and is just as intimately con- 
nected with the other parts of this system as are 
the thyroid, pituitary, ovaries or any other of the 
ductless glands; hence if disorders which are de- 
pendent upon emotional disturbances really have 
an internal secretory basis, it is obvious that very 
few functional troubles in women are not in that 
category of disturbances now being differentiated 
and called ''endocrine disorders." Practically all 
such conditions are in a greater or less degree 
amenable to organotherapeutic procedures, and the 
more these are applied in clinical practice, the more 
are we convinced of the importance and extent of 
this comparatively new class of disorders. 

It is difficult intelHgently to discuss a subject as 
broad as neurasthenia. First of all it is not really 
an entity, but rather a symptom-complex with vary- 
ing manifestations. While it is found in both 
sexes, it is much more common in women, and most 
frequently is connected in some way with one or 



IN PRACTICAL MEDICINE 103 

more disorders of the sex apparatus. When a pa- 
tient comes to us with a combination of symptoms 
which the cHnical history seems to connect with a 
menstrual disorder, deranged or misused repro- 
ductive functions, chmacteric irregularities or a 
general run-down condition, if there is a nervous 
element in the case — and in how few is there not? 
— it is very easy to call it neurasthenia. 

As a matter of fact it is impossible not to have 
neurasthenia in patients who are below par, for 
when an individual is asthenic and debilitated, the 
nervous mechanism is likely to be just as asthenic 
as the muscular system, the eliminative system or 
the endocrine system; and when we meet women 
who are hysterical or melancholic; excitable or 
apathetic; menstrually plus or minus (if I may use 
such a term) ; or are suffering in some way as a 
result of an over- or under-activity of the genital 
organism, we might better consider them from the 
standpoint of the internal secretions rather than to 
classify them as neurasthenics and give them tonic 
or sedative treatment according to the exigencies 
of each case. 

I have come to the conclusion that it is not pos- 
sible to treat functional gynecological disorders ef- 
fectively without in every case carefully consider- 
ing each individual from this standpoint. The duct- 
less glandular system in women is as sensitive to 
physiologic impressions as the nervous system; 
hence one must expect to encounter pluriglandular 



104 THE INTERNAL SECRETIONS 

disturbances very frequently. The principal rea- 
son that this does not seem to have been done more 
often is because the subject has not yet reached 
that stage of stabiHty which some physicians insist 
upon. You know that there are still members of 
our profession who deny the "hormone theory/' as 
they like to call it; and with this, of course, they 
virtually deny the feasibility as well as the appli- 
cability of organotherapy. It is to be hoped that 
everyone present this evening is safely out of this 
class, and that all will admit with me the probable 
relationship of ductless glandular disorder with the 
majority of those cases usually called "neuras- 
thenics." If so, a few suggestions of a therapeutic 
nature may be acceptable, and the discussion which 
follows doubtless will bring out considerably more 
of practical value than does this paper. 

There is a comparatively small number of women 
whose neurasthenic manifestations are associated 
with ovarian and menstrual superactivity. Their 
periods are prolonged and excessive, they have so 
little freedom from the inconveniences of menstru- 
ation and their economy is so depleted by the undue 
loss of blood and strength, that they easily become 
neurasthenic. Often they brood over their condi- 
tion; and, rarely, the onset of a heavy flow pros- 
trates them not merely physically but mentally. All 
too often these cases are called ''endometritis" for 
convenience and are treated surgically with medi- 
ocre results; while many might be benefited by the 



IN PRACTICAL MEDICINE 105 

exhibition of mammary extract. This substance 
antagonizes ovarian activity, depletes the uterine 
vessels and is an excellent means of controlling 
functional uterine hemorrhage. Incidentally it has 
been given v^^ith good results in uterine fibroids, not 
only stopping the hemorrhage but, in an encour- 
aging proportion of cases, reducing the size and 
stopping the growth of the tumor. But this is tak- 
ing us from the subject of the evening. Mammary 
extract is given in 5-grain doses, preferably at 
meals. Ten grains three times a day is usually the 
maximum and if this is continued for two or three 
weeks, then omitted during the days free from men- 
strual flow and started again, and if necessary 
pushed, during the flow, to be discontinued again 
till the next menses and given in this manner for 
two or three months, the efifects of the increased 
ovarian activity will be reduced and the benefit will 
usually embrace other symptoms than the one for 
which mammary therapy originally was instituted. 

A larger number of neurasthenic women exhibit 
the opposite pelvic conditions, and suffer from de- 
layed or insufficient menses. This is but one symp- 
tom in a chain of disorders due to hypoendocrinism 
(hypocrinism) — reduced internal secretory activity 
and one which gives us an excellent opportunity to 
apply the principles of organotherapy, and not only 
remove the menstrual disabilities but with them the 
associated neurasthenia. Such individuals are usu- 
ally anemic, insufficiently nourished and toxic. 



106 THE INTERNAL SECRETIONS 

They are flabby, often obese and do not react well 
to the morning bath (which, by the way, very few 
of them take) or to treatment of any kind. Their 
cells are physiologically lazy and asthenic (al- 
though they may be mentally bright and despite 
their troubles may attempt to be quite active phys- 
ically). Yet always associated with these common 
conditions there is a more or less marked nervous 
element which is usually singled out and given un- 
due prominence in the nomenclature as well as the 
therapeutics, for, of course, such cases are obvi- 
ously "typical cases of neurasthenia." 

The cellular inactivity of such individuals almost 
invariably indicates a condition of minor hypothy- 
roidism, in fact this disorder may be the principal 
basic cause of the whole trouble, for it is surprising 
how many times the thyroid may be responsible for 
functional disorders of many kinds. (By the way, 
this statement is not made thoughtlessly; for many 
functional cellular disabilities can either be traced 
to hypothyroidism or shortly after the onset are ag- 
gravated by an associated thyroid inadequacy; and 
while in some cases other factors may be predomi- 
nant, to the seeing eye there is usually a path of 
more or less prominence which leads to the thyroid 
mechanism). This hypothyroidism, in turn, may 
cause a reduced luteal activity and when it is suffi- 
ciently marked to be clinically evident, many of the 
endocrine glands are already working at half speed 
or even slower. This explains the good results fre- 



IN PRACTICAL MEDICINE 107 

quently obtained from pluriglandular therapy in 
such cases, of which more shortly. 

This action is strictly speaking a reflex action, 
and the use of this term needs a brief qualification. 
It may be and probably is nervous, but it is also and 
more decidedly hormonic in origin. The thyroid 
produces an internal secretion which stimulates the 
ovaries and their corpora lutea, hence a "reflex" 
influence of reduced thyroid action is a correspond- 
ingly reduced luteal action, and so on. This means 
that there may be cases of amenorrhea of distinct 
thyroid origin; and it is of interest to recall that 
Prof. Dalche, of Paris, regards amenorrhea and es- 
pecially dysmenorrhea in young women, as defi- 
nitely due to thyroid rather than ovarian disorder. 
He reports the successful treatment of many cases 
of this character by giving thyroid alone, the dose 
usually being 1 or 2 centigrams per day in divided 
amounts. 

By far the greatest number of menstrual neuras- 
thenics, as well as practically all sexual neuras- 
thenias in women, have their origin in a functional 
derangement of the internal secretory portion of 
the ovaries. This, of course, is the corpus luteum, 
although the ovarian stroma has been shown to 
exert a certain but minor influence of this nature. 
Since the development of a corpus luteum is sup- 
posed to be synchronous with the onset of menstru- 
ation, per contra, the absence or semi-absence of 
the menses is often due to a decreased production 



108 THE INTERNAL SECRETIONS 

of the luteal hormone. This disturbs the delicate 
hormone balance, already referred to, and is di- 
rectly concerned in bringing about certain neuras- 
thenic manifestations, at the same time reflexly 
(hormonically) producing a vicious circle. 

The whole subject is being studied experiment- 
ally in several laboratories and many hundreds of 
clinical applications are being made from week to 
week, although but a small number of them are re- 
ported for the benefit of the profession. It may be 
said unequivocally that there is an incontestible re- 
lation between the physiologic action of the corpora 
lutea and neurasthenia. Howard Kelly and C. H. 
Burnham of Baltimore have established this on a 
practical basis and have reported a number of cases 
of typical neurasthenia in women, which were suc- 
cessfully treated with lutein. R. T. Frank of New 
York, Adam Leighton of Portland, Me., Paul Car- 
not of Paris, W. Blair Bell* of Liverpool and sev- 
eral others that I might mention, have expressed 
themselves on this subject, and we cannot but con- 
clude that not only is neurasthenia frequently due 
to functional disturbances in the hormone produc- 
tion of the ovaries, but that it may also respond fa- 
vorably to suitable doses of luteal preparations. 

In passing it may be well to mention briefly a 



*I feel it a privilege to add here that my friend Dr. Blair 
Bell recently has published a book entitled "The Sex Complex" 
(Bailliere, Tindall & Cox., London, or Wm. Wood & Co., New 
York), in which the relation of the internal secretions to the 
female economy is taken up in a masterly and interesting 
fashion. 



IN PRACTICAL MEDICINE 109 

form of neurasthenia accompanied by dysmenor- 
rhea in women near the menopause. These cases 
are usually obese and metabolism is invariably re- 
duced. Lemaire of Paris believes that most cases 
of this character are due to a disturbed equilibrium 
between the internal secretory glands, and he 
recommends in such cases the administration of 
combinations of thyroid and luteal substances. In 
his experience he finds that this treatment not only 
reduces the pain and discomfort at the menses, but 
also enhances the metabolism and many times con- 
trols the distressing neurasthenic manifestations. 

Another of the ductless glands likely is con- 
cerned in many cases of neurasthenia in women. 
The pituitary body and its various distinct parts 
are not so well understood as the thyroid or the 
corpus luteum; but the hypophysis is none the less 
a part of the endocrine system and as such exerts 
some influence upon such a broadly extending com- 
plexity as neurasthenia. Neurasthenia is not in- 
frequently a side-issue in cases of dyspituitarism 
and as we have opportunity to study more closely 
these relations in women with pituitary disease, we 
will be able to speak with more authority on this 
phase of the subject. From a practical standpoint 
we do know, however, that the administration of 
total pituitary substance has a beneficial and quite 
general tonic influence, especially in those indefi- 
nite, asthenic cases where the nervous and muscu- 
lar efficiency seems to be especially deficient. As 



no THE INTERNAL SECRETIONS 

an empirical remedy in such cases, as well as in 
certain pluriglandular insufficiencies, pituitary sub- 
stance (whole gland) is helpful because of its tonic 
action upon cardiac, intestinal and uterine muscles; 
and while there still may be only slight scientific 
ground for giving it in many cases, it is of un- 
doubted clinical value, and when an eminent man 
like Leonard Williams, of London, expresses his 
faith in pituitary as a remedy for amenorrhea and 
menstrual neurasthenias, I am content to believe 
without the ''incontestible scientific proof" that 
some physicians still insist upon — in public! Inci- 
dentally I would like to ask how it is possible to 
establish a subject relating to therapeutics upon 
this hypothetical plane of indubitability without a 
certain amount of clinical experience; and if we are 
to refrain from empiricism, how are we to progress? 
This same Leonard Williams has also found 
pituitary of value in those cases he amusingly calls 
''the moth-eaten old ladies who come out of board- 
ing houses to go to church"; and it will also be 
found useful in the elderly, inactive, neurasthenic 
women who, perhaps, are not always found in this 
same rare category. In a paper read before the 
Royal Society of Medicine, which I had the pleasure 
of hearing some years ago, WilHams spoke favor- 
ably of a pluriglandular preparation called hormo- 
tone, which is a combination of the three glands 
mentioned this evening — thyroid, pituitary and 
ovaries. In my own limited experience I have found 



IN PRACTICAL MEDICINE 111 

this frequently superior to corpus luteum alone 
(save only in cases where the ovaries have been 
removed and cannot therefore respond to the homo- 
stimulant action of the luteal ingredient) ; and it 
has the advantage of costing considerably less, for 
unfortunately corpus luteum is still an expensive 
remedy and the recent increased demand seems to 
be making the price go up, rather than dov^n, as 
one might presume. At all events I have seen good 
results from this combination in neurasthenia in 
women. 

In cases with amenorrhea the increased action of 
the thyroid and ovaries not uncommonly has re- 
established the flow and associated nervous mani- 
festations due solely to the repression of this func- 
tion, were also controlled. In the nervous mani- 
festations of the artificial menopause, especially in 
comparatively young women, it is not so effective 
unless corpus luteum is given with it, in the pro- 
portion of 5 grains of corpus luteum to one or two 
tablets of hormotone, three times a day. In dys- 
menorrhea occasionally it has stopped the pain al- 
most like a sedative drug, while again in seemingly 
identical cases it has seemed to be quite inert. (Par- 
enthetically this is not an uncommon experience in 
organotherapeutic practice.) One cannot always 
depend upon similar results from the same treat- 
ment in presumably similar cases. The influence 
of these hormone-bearing preparations is rarely di- 
rectly due to the action of the principles they con- 



112 THE INTERNAL SECRETIONS 

tain, but rather to the results of their homostimu- 
lant action; i. e., to the increased activity of the 
glands which they stimulate and the enhanced hor- 
mone production. Perhaps an explanation of this 
somewhat discouraging experience lies in lack of 
persistence, for not always are the ductless glands 
as easily stimulated, while in some of the rapid- 
acting cases the startling results are brought about 
because the missing but all essential touch is given 
to the pendulum, and it starts again. 

In the nervous and circulatory disturbances of 
the menopause pluriglandular therapy is worth try- 
ing, for these symptoms are in most cases naught 
save the natural results of the removal of stimuli to 
which the body has accustomed itself for thirty 
years or more. 

There are other phases of this subject which will 
occur to you. In some cases the endocrine element 
will be very apparent when one is looking for it; 
while in others it is not easy to demonstrate. In 
such cases, however, it is there none the less and I 
prefer to imagine that this unnoticed factor is play- 
ing some minor role, and that the more obvious 
manifestations of diagnostic value have not yet be- 
come sufficiently marked to be differentiated. 

In conclusion, the administration of thyroid, cor- 
pus luteum or pituitary gland, or combinations of 
them, to my mind is as rational a form of the treat- 
ment of many of the functional neuroses in women, 
including neurasthenia, as one could hope for. Of 



IN PRACTICAL MEDICINE 113 

course, such remedies do not militate against the 
hygienic procedures or even drugs that may seem 
to be indicated, on the contrary one will often find 
that organotherapy renders the response to other 
treatment much more satisfactory. 

In applying the principles of endocrinology in 
the consideration and treatment of neurasthenia in 
women, we are removing obstacles and assisting 
Nature; and where this is accomplished one can 
expect with much more confidence than otherwise, 
that Nature will be better able to bring about the 
much-to-be-desired outcome. 



X 

SEX DISABILITIES CONSIDERED AS 
ENDOCRINE DYSCRASIAS 

EACH part of the endocrine system depends 
upon and influences each other part. Each of them 
is indispensable to the organism, though experi- 
mentally it has been shown that life is not neces- 
sarily terminated by the removal of one or more 
of these essential organs, though we know that the 
adrenal glands and the parathyroids are quite nec- 
essary to life. 

Not least in importance among these "glands of 
life" are the gonads, and while their physiological 
importance to the economy as a whole is admitted, 
it sometimes seems that it is not appreciated, at 
least in therapeutics. There is no longer a question 
as to the internal secretory capacity of both ovaries 
and testes, nor can there be any doubt of the im- 
portance of their chemical messengers. Neverthe- 
less it is a common thing to discover sex disabilities 
that have not been considered as endocrine dys- 
crasias, and more than often in consequence have 
been treated without success. The ''bad name" 
given to the particular form of therapeutics inaug- 
urated immediately following Brown-Sequard's 
epoch-making announcement before the Paris Bio- 
logical Society in June, 1889, was not deserved and, 
like the baneful effects of gossip, persisted long 
after its inherent value had been firmly established. 
(114) 



IN PRACTICAL MEDICINE 115 

To the writer at least the method of treatment 
inaugurated by Brown-Sequard is rational because 
it is resultful. The personal experiences of this 
distinguished savant must be considered as well 
founded for the treatment was administered to 
himself in a scientific laboratory where the study 
of physiology was uppermost and under circum- 
stances most favorable to calm and judicious con- 
sideration of the findings. And the experience of 
Brown-Sequard has been duplicated time and again 
for over thirty years. 

Sex disabilities must needs be considered as re- 
sulting from internal secretory disorder because 
the sex manifestations are so absolutely under the 
regulation of the endocrine system. Not merely do 
the gonads bring about their subtle influences upon 
feature, form and function; but they themselves are 
played upon by the other ductless glands, and I do 
not think that there is a single endocrine disturb- 
ance affecting any of the glands of internal secre- 
tion that does not have in its syndrome some direct 
or indirect effect upon the gonads and their work. 

The thyroid, best known of the glands of internal 
secretion, certainly exerts its influence upon the de- 
velopment and functional value of the ovaries or 
the testes, for the cretin is never sexually developed 
and the sufferer from myxedema acquires with the 
myxedematous characteristics typical changes in 
the sex manifestations which undoubtedly are due 
to the modified thyroid chemistry. The lack of the 



116 THE INTERNAL SECRETIONS 

thyroid hormone predicates gonad insufficiency.* 
The opposite happens to be equally true, for hyper- 
thyroidism is not uncommonly associated with 
hyperovarism, menstrual difficulties and, occasion 
ally, erethism. Pelvic congestion is not an uncom- 
nion accompaniment of hyperthyroidism as every 
gynecologist well knows. 

The pituitary gland is none the less intimately 
connected with the sex glands, and the best known 
forms of pituitary disease have as prominent clin- 
ical features, functional or even structural changes 
in the gonads. Hypopituitarism is sometimes 
called "dystrophia adiposo-genitalis" because the 
dystrophy makes itself so manifest in the genital 
form and function. Insufficiency of the pituitary 
gland spells genital insufficiency, while possibly 
pituitary excess may cause a temporary increased 
genital function, though this is not so common as 
in the opposite condition; and, too, it must be re- 
membered that hyperpituitarism very commonly 
metamorphoses into hypopituitarism and this may 
account for the asexual manifestations occasion- 
ally seen in individuals with well defined changes 
due to an obvious pituitary excess. 

The adrenal glands are also connected with the 
gonads, though there is not so much clinical data 
on this phase of endocrinology as in the study of 
the thyroid or pituitary glands. Nevertheless the 



*And sex deficiencies should lead one to look for evidence 
of thyroid and other endocrine symptoms. 



IN PRACTICAL MEDICINE 117 

profession is now fairly unanimous that certain 
sexual complications have an adrenal origin, for 
instance the peculiar organic and functional 
changes called 'Virilism" in which the female char- 
acteristics are supplanted by obvious masculine 
characteristics, have been shown by Apert, Ballet, 
Tuffier and others to be the result of organic ad- 
renal disorder. On the other hand Addison's dis- 
ease is practically always accompanied by impo- 
tence. The functional form of adrenal insufficiency 
discussed in Chapter VII may be expected to be 
accompanied by some sort of sex depression, for 
the asthenia of hypoadrenia cannot well affect so 
many functions — circulation, muscular power, men- 
tal activity, etc. — without some influence upon the 
gonads. I have had several experiences which sup- 
port this view and have had a number of illustrative 
cases brought to my attention. The case of ovarian 
poisoning referred to on page 86 is one. The case 
of shock following the ''near accident" mentioned 
on page 74 is another. I heard of a physician 
who had been impotent for a year or more follow- 
ing an accident, whose hormone balance had been 
severely disorganized and whose blood pressure 
and other clinical evidences indicated a state of 
chronic hypoadrenia. Tonic hormone therapy re- 
stored this balance in a short time. In the chapter 
on shell shock (VI) I might have added that this 
condition is practically always associated with evi- 
dence of disturbances in the sex manifestations. 



118 THE INTERNAL SECRETIONS 

There is much evidence in favor of the sugges- 
tion that sex disabihties may be associated with or 
due to dyscrinism, and that the adrenal system, so- 
called, is intimately functionally related with the 
sex glands. 

The relation of the thymus to the sex glands is 
now fairly well understood, and it has been shown 
that a persistent thymus is likely to be the cause of 
genital insufficiency, for the thymus itself produces 
a chemical antagonist to the gonads and as soon as 
it normally atrophies just before puberty, the sex 
glands are thus permitted to assert their chemical 
or hormonic functions. 

Several of the clinical reports in comparatively 
recent literature indicate that parathyroid disease 
also exerts its influence upon the sex glands. While 
Parkinson's syndrome or paralysis agitans is not 
admitted by all to be a distinct parathyroid dis- 
order, there is a good deal of evidence in favor of 
this position, and I have encountered not merely 
good results following the parathyroid method of 
treatment of this disease, but have seen the sex dis- 
ability which is a part of the syndrome materially 
modified for the better following a longer or shorter 
course of parathyroid treatment. 

At present the pineal is not supposed to be a 
gland of internal secretion although from my own 
standpoint it is difficult to explain many of the find- 
ings connected with epiphyseal tumors on any other 
basis than that of internal secretion. At all events 



IN PRACTICAL MEDICINE 119 

hyperpinealism has been shown to be accompanied 
by a very remarkable early ripening of the sex 
glands, and precocity both mentally and sexually. 
Whether this is of endocrine origin or not, it is a 
matter of considerable clinical interest. 

With these briefly outlined facts in mind, we can 
not but conclude that the disabilities of sex always 
deserve consideration from an internal secretory 
standpoint. Dysgenitalism is dyscrinism, and clin- 
ically as well as therapeutically this position can be 
established beyond peradventure. Many a case of 
obscure neurasthenia will be found to be accom- 
panied by a sexual neurosis which is really the bot- 
tom of the whole matter. Indeed, I am convinced 
that much of the success following pluriglandular 
therapy as outlined elsewhere,''' is largely due to a 
re-establishment of an unappreciated dysgenital- 
ism. Many forms of organotherapy are know^n to 
affect genital function. Thyroid extract has been 
used time and again to control menstrual disorders. 
Its use has been equally efficacious in re-establish- 
ing a more nearly normal sexual development and 
activity in individuals suffering from both major 
and minor thyroid insufficiencies. The orthodox 
treatment of the Froehlich syndrome (dystrophia 
adiposo-genitalis) is pituitary feeding, and one of 
the therapeutic results is a favorable modification 
of sexual development and function. In fact pitui- 
tary feeding is beginning to be used with moder- 



*See Chapters V, VI, VIII and IX. 



120 THE INTERNAL SECRETIONS 

ately good results in sexual insufficiencies not nec- 
essarily connected with well marked pituitary dis- 
ease, and quite recently Stelwagen (N. Y. Med. 
Jour., 1917, ciii, 879) reports the successful treat- 
ment of a number of cases of functional impotence 
with 15 or more grains of anterior pituitary gland 
administered daily for a period. It is granted that 
this is a preliminary report, but at least it is a sug- 
gestive experience as we consider the particular 
subject under discussion. 

Quite the most important phase of organother- 
apy in dysgenitalism is the use of extracts of or- 
gans corresponding to those affected — the ovaries 
or testes, as the case may be. 

Corpus luteum has established itself as a stand- 
ard remedy in many functional genital disturbances 
in gynecological practice, and its value is referred 
to elsewhere in this book; but somehow or another 
the corresponding treatment in the male still re- 
mains ''under a cloud." The physician who would 
champion luteal preparations without a question, 
says little about the use of testicular preparations; 
and there is a very obvious question about this in 
the minds of the majority of the profession. 

Despite this I have the utmost confidence in this 
phase of organotherapy. I believe that Brown- 
Sequard's findings were based upon good physiol- 
ogy and were not overstated, and while we will 
grant that there undoubtedly were many overstate- 
ments in the nineties, especially by the aggressive 



IN PRACTICAL MEDICINE 121 

quacks who seized upon Brown-Sequard's reports 
to fleece their gullible patients, this does not change 
the fundamental basis of reason for testicular or- 
ganotherapy. 

If functional impotence in the male as well as in 
the female is considered in the light of an endocrine 
dyscrasia, there is more hope of a successful out- 
come than from all the electrical, mechanical and 
psychotherapeutical procedures combined. The 
principle of homostimulation oft referred to in my 
writings applies just as much to the gonads as to 
the thyroid, pituitary or any other gland of in- 
ternal secretion, and the clinical results following 
the use of Didymin, Sequarine, Hormotone, or the 
Roberts-Hawley Lymph, or any other preparation 
calculated to stimulate the sex glands to a greater 
functional activity, are based upon good physiology 
and sound reasoning, many statements to the con- 
trary, notwithstanding. This is not the place for 
case reports. I have mentioned one or two previ- 
ously and could extend the list materially. 

Let us consider for a moment the philosophy 
of the last of these proprietaries. Unnumbered 
cases of so-called ''incompetence" have been treated 
with this lymph. I have personally used it in my 
practice and am certain that this homostimulant 
action is the physiological explanation of the good 
results that one can expect to secure following its 
judicious use in cases of this character. I am equally 
convinced that the empirical administration of the 



122 THE INTERNAL SECRETIONS 

preparation Hormotone, or Tabloid Mixed Glands, 
in dysgenitalism is active through the augmented 
internal secretory activity of the gonads v^hich thus 
may be brought about. 

The beneficial effects from this kind of treat- 
ment seem to originate from the augmented gonad 
activity for this alone is sufficient to increase met- 
abolism, to create force (the testicular hormone has 
been called "a dynamogenic hormone") and to 
start up a greater degree of functional activity in 
the other interrelated endocrine organs. This ac- 
counts for the unusual effects that have been re- 
ported following the use of the R-H Lymph in very 
chronic and much treated cases ; as vvrell as the more 
direct effects on impotence and hypogonadism. 

I realize that statements such as the foregoing 
are open to criticism and that they w^ill be criticised 
just as similar ones have been critized for thirty 
years, but the opinions of critics count for naught 
as compared with the opinions of satisfied patients; 
and nothing can shake my belief that one is more 
likely to accomplish the desired therapeutic ends in 
the treatment of sexual disabilities if they are con- 
sidered as endocrine dyscrasias and treated as such. 



XI 



THE RELATION OF THE INTERNAL SE- 
CRETIONS TO RHEUMATISM AND 
THE RHEUMATIC DIATHESIS 

RHEUMATISM and the rheumatic diathesis 
are conditions concerning which the medical pro- 
fession holds numerous and widely differing views. 
The literature regarding the various phases of 
rheumatism is as extended as it is contradictory. 
The unsuspecting reader frequently is led into a 
morass of differing conceptions from which it is 
not always the easiest thing to extricate himself. 

Some writers insist that ''rheumatism," and by 
that they usually include the varying disorders 
which have been classed under this name, is a mani- 
festation of digestive trouble pure and simple; cor- 
rect the digestion and the rheumatism will be auto- 
matically taken care of. 

Others insist that it is essentially the result of 
an imperfect mineral metabolism and assure the 
reader that recourse to certain inorganic neutral- 
izing remedies will quickly bring conviction regard- 
ing the correctness of this view. 

Still others assert that there is a bacterial origin, 
not only for the obviously infective forms of rheu- 
matism, but for all of them; and that the successful 
treatment of this disorder is not complete without 



Prepared for a "Special Rheumatism Number" of American 
Medicine (New York), published June, 1915. 

(123) 



124 THE INTERNAL SECRETIONS 

at least the addition of procedures based upon its 
"undoubted microbic origin." 

Much has been written regarding the relation of 
uric acid to the rheumatic diathesis and opinions 
seem to be veering away from the statements so 
ably presented by Dr. Alexander Haig. In a recent 
communication (Interstate Med. Jour., April, 1915) 
Goodman aptly remarks that: ''The uric acid the- 
ory is at present tottering on its unstable founda- 
tions and we are growing more and more inclined 
to the view that not uric acid, but rather disturb- 
ances of intermediary purin metabolism, are at the 
root of the evil." 

Looking at this problem from the standpoint of 
an average physician, it is altogether probable that 
there is an element of truth in all of the theories 
regarding rheumatism and that the statements 
which serve as a prelude to this article are all cor- 
rect to a certain degree. None can deny that rheu- 
matism in the majority of instances exhibits as one 
of its most constant manifestations a disturbance 
of metabolism, and considerable evidence is accru- 
ing to indicate that not a few of these cases have 
as the original basis of the trouble an obscure in- 
fective process which may never be so obvious as 
to direct attention to itself, but is only brought to 
light following the empiric use of stock vaccines 
given with the expectation that this unnoticed in- 
fection may be present. In such cases (and Sher- 
man, of Detroit, has frequently directed attention 



IN PRACTICAL MEDICINE 125 

to the importance of this class) the diagnosis is 
often made by the cHnical results of the empirical 
treatment and it may be stated in unqualified terms 
that many of the chronic rheumatic affections are 
of bacterial origin, even though they may show 
none of the typical findings of obviously infective 
cases. 

The manifestations of the rheumatic diathesis 
are too frequently associated with digestive dis- 
turbances for the consistent physician to deny the 
intimacy of this relation, and it is not an uncom- 
mon thing for dietetic regulation, with attention to 
the inevitable defective elimination resulting from 
disturbed digestive activity, to bring about a com- 
plete control of the rheumatic phenomena. Certain 
it is that the excessive amounts of protein which 
are so commonly eaten combine with other factors 
to bring about the metabolic chaos which is so usu- 
ally called rheumatism. Parenthetically, it might 
be remarked, these persons are not suffering from 
the results of mineral excess, although the labora- 
tory evidence may seem to indicate this; rather 
they are undergoing their tortures because of a 
lack of the natural mineral elements — the vegetable 
alkalies — which the body needs, and which they 
could just as well have if their diet included more 
of such articles as potatoes, greens and cereals, and 
less meat. 

Whether or no the initial cause is dietetic or bac- 
terial in origin there can be no doubt that all forms 



126 THE INTERNAL SECRETIONS 

of rheumatism are evidences of essential changes 
in the chemistry of the body and, this being 
granted, should not the regulators of metabolism 
be considered both in the etiology as well as in the 
treatment of the various forms of this disorder? 

It should be quite unnecessary to lend emphasis 
to the importance of the glands of internal secre- 
tion as regulators of the functions of the body. The 
hormones not only control, but correlate these vari- 
ous cell activities, and their work is so closely con- 
nected with the factors which are concerned in the 
reaction of the body to the causes of rheumatism, 
as well as to the attempts made to cure this condi- 
tion, that the physician who considers the relation 
of the internal secretory glands and their hormones 
to rheumatism is more likely to solve some of its 
mysteries than the one who overlooks them en- 
tirely. 

It is remarkable how close a relationship may be 
discovered between certain of the ductless glands 
and the symptoms which have come to be consid- 
ered pathognomonic of rheumatism. Presuming 
for a moment that the various manifestations of the 
rheumatic diathesis are toxic in origin, is not de- 
toxication essentially controlled by certain of the 
endocrine glands? 

If the infective origin of rheumatism is admitted 
to be the most frequent or important, then we must 
also admit that certain of these remarkable organs 
are responsible for the production of the protective 



IN PRACTICAL MEDICINE 127 

measures which the body automatically brings into 
play in infections. Sir Almroth Wright himself 
insists that all the substances concerned in the con- 
trol of infections must be considered as products 
of the internal secretory organs. 

If functional digestive disturbances are the most 
common basis for this condition, then it is proper 
to consider the relation of the alimentary hormone, 
secretin, to this disease and, where digestive in- 
sufficiencies are manifestly present, recourse be 
had to the use of secretin as a remedy, for I am 
thoroughly convinced of its value as a physiologic 
means of stimulating lazy or inactive digestive 
glands, statements to the contrary notwithstand- 
ing. So whether rheumatic conditions are purely 
metabolic in origin, or whether they are due to 
micro-organisms, or to indigestion, we must not 
belittle the fact that in any event there must be a 
role that the internal secretory organs play which 
favors their prevention as well as the cure. 

Under the present circumstances it would be 
quite difficult to consider this from the protective 
or prophylactic standpoint. Rheumatism is too in- 
sidious a disease. Its onset is of such a nature that 
it is not appreciated until one or more of the more 
definite manifestations — joint pain, immobility, 
swelling, etc., — brings the patient to his physician. 
We can, however, make good use of this informa- 
tion in the diagnosis and treatment of rheumatic 
conditions. For example, too often the orthodox 



128 THE INTERNAL SECRETIONS 

treatment with salicylates or other neutralizing 
agents, does not give the desired degree of results, 
or merely tides the patient over whilst the dis- 
turbed chemical conditions are under the influence 
of the drugs or measures used. After a longer or 
shorter time the patient has a recurrence and un- 
fortunately, too often it is more severe than the 
initial attack. In such cases the knowledge that 
the ductless glands may be frequently concerned 
in rheumatism will enable the physician to con- 
sider the case from a slightly different angle, one 
which I regret to say is rarely taken by the medical 
profession, and this new viewpoint may facilitate 
the control of future manifestations. It will also 
open up the possibilities of certain forms of or- 
ganotherapy which, rightly applied, may materially 
influence the response of the organism to the other 
usual therapeutic procedures. Right here it should 
be emphasized that organotherapy is not recom- 
mended as the sine qua non in the treatment of 
rheumatic affections. Far be it from such, but as 
an important adjuvant and a phase worthy of con- 
sideration it deserves considerably more attention 
than it has previously received, as may shortly ap- 
pear. 

Leopold Levi, of Paris, insists that the thyroid 
is quite intimately connected with both the cause 
and, in certain cases, the successful treatment of 
various joint conditions, not excluding the most se- 
rious form, arthritis deformans, and in the intro- 



IN PRACTICAL MEDICINE 129 

duction to his recent book ("La Petite Insuffisance 
Thyroidienne et son Traitement") he makes the fol- 
lowing statement: ''Therapeutics is very helpful 
in the study of minor hypothyroidism for it reveals 
several stigmata of this condition which otherwise 
might be overlooked. For example, in March, 1905, 
we made the first application of thyroid therapy, 
aside from the treatment of myxedema, in a sub- 
ject suffering with chronic rheumatism compli- 
cated with psoriasis. The first noted effect con- 
sisted in an increase in the appetite; the second re- 
sult was a reduction in the marked feeling of cold 
which happened to be present (this sufferer was 
astonishingly cold and lived in a degree of heat that 
was altogether preposterous). Strangely enough 
the thyroid therapy made a marked diminution in 
this pecularity and also benefited the rheumatism. 

*'The form of treatment applied in other cases of 
chronic rheumatism also directed our attention to 
a certain degree of benefit upon constipation.'' Else- 
where in the same book the author connects thyroid 
disturbances with rheumatic manifestations and 
quotes a large number of reports to the effect that 
"the reality of the thyroid causes of chronic rheu- 
matism is incontestable. Its existence depends in 
many cases on thyroid lesions." 

Chronic rheumatism is quite common in subjects 
presenting signs of hypothyroidism and it is well 
known that rheumatic manifestations may be asso- 
ciated with or aggravated by incidents in the meno- 



130 THE INTERNAL SECRETIONS 

pause. Frequently rheumatic manifestations fol- 
low thyroid atrophy due to pathological conditions 
or following thyroidectomy for Graves's disease, 
but the most important proof is the fact that the 
use of thyroid extract in many cases ameliorates 
rheumatic manifestations. 

Thyroid therapy may be applied frequently in 
the treatment of various forms of arthritis with 
very good success. There are a number of papers 
recording and attempting to explain its remarkable 
results in various forms of chronic rheumatism. 
Probably the most comprehensive of all these com- 
munications is that of Leopold Levi who reports 
three hundred cases treated under his direction dur- 
ing a period of eight years. This investigator, who 
is well known to those who have read the litera- 
ture on the thyroid gland, differentiates a form of 
rheumatism which is due to what he terms thyroid 
instability. The disease is found in relatively young 
persons, is only slightly deforming, and usually af- 
fects the smaller joints. It seems to progress by 
fits and starts. In these cases the joint disturb- 
ances are by no means the only troubles. Occa- 
sionally there are other manifestations of thyroid 
disorder sometimes evidently due to increased thy- 
roid activity and at other times, the majority of 
cases it may be noted, the result of decreased thy- 
roid activity. 

The manner in which this form of rheumatism 
responds to treatment varies considerably with the 



IN PRACTICAL MEDICINE 131 

associated manifestations. In the juvenile form, 
where there is no very serious deformity, the re- 
sponse to treatment is good, and while the serious 
chronic and so-called "incurable" cases do not re- 
spond as rapidly to this treatment, there is no 
doubt that persistent thyroid therapy causes a very 
decided benefit. Levi concludes that in many cases 
of chronic rheumatism thyroid extract is "s, pre- 
cious remedy," securing an average of results that 
is very encouraging, and occasionally producing 
astonishing changes for the better. According to 
this writer: "Thyroid therapy should be placed in 
the first rank of the therapeutic armamentarium in 
the treatment of chronic rheumatism." He recom- 
mends a daily dose ranging from .05 to .30 grammes 
(1 to 5 grains) in divided doses. The average is 
1/^ to 3 grains per day and it must be continued 
for as long as six months. 

The mechanism of the action of thyroid extract 
in certain conditions has for some time been in 
doubt; and this is especially true as far as its influ- 
ence in rheumatism has been concerned. This ex- 
tract, above all others, has been considered one of 
the best means of enhancing cell activities and in- 
creasing the metabolic exchanges. Since the met- 
abolism in rheumatism is much below par, any ad- 
vantage that accrues from thyroid therapy might 
be considered as due to this efTect upon the cells. 

A scientific explanation of this may be gathered 
from some interesting experiments by Slosse who 



132 THE INTERNAL SECRETIONS 

was professor of physiology at the University of 
Brussels before the war. He has carried out a num- 
ber of experiments both in the laboratory and in 
the clinic to connect the disturbances of nitrogen- 
ous metabolism with the work of the ductless 
glands and as a result of his investigations he states 
that under normal circumstances the thyroid gland 
secretes a "hormone de desamination'' — a deamin- 
izing hormone — which influences the nitrogenous 
exchanges and when deficient causes a reduction of 
the power of the cells throughout the whole organ- 
ism to split up the albuminoid substances, espe- 
cially the nucleo-albuminoids, from which uric acid 
and other substances of the purin group are formed. 
Theoretically then, the enhancement of thyroid ac- 
tion should favor nitrogenous metabolism, and a 
large series of urinalyses made by Slosse and his 
associates substantiates this. The favorable clin- 
ical experiences which have been recorded by a 
number of French writers in a measure may be ex- 
plained by these findings. 

There is another form of chronic rheumatism 
somewhat similar to that which reacts to thyroid 
therapy. Like it, it is of endocrine origin, but in- 
stead of being due to thyroid insufiiciency, it is a 
result of ovarian insufiiciency. This is the rheuma- 
tism which appears in women after the menopause 
and it may be quite possible that its etiology is 
partly due to thyroid disturbances. At least it re- 
acts more quickly to luteal therapy, especially if 



IN PRACTICAL MEDICINE 133 

this procedure is applied early in the course of the 
disease. Dalche reports that the administration 
of ovarian substance has given very good results 
in such cases, and in suitable cases he occasionally 
combines thyroid and luteal substance. 

It is difficult definitely to state which case of 
rheumatism is of thyroid origin and which is not. 
According to Leopold Levi and de Rothschild the 
only way to answer this question is empirically to 
apply thyroid extract, and in explanation of this 
they may be quoted as follows : ''From the prac- 
tical point of view, in all forms of rheumatism in 
which the cause is unknown, it is an advantage to 
apply thyroid therapy. In such cases there will be 
more chance of results if the subject is young, if 
the rheumatism is accompanied by subacute ex- 
acerbations, and if there is only slight deformity. 
In those cases where there is a decided thyroid in- 
fluence the initial results will be rapid, sometimes 
immediate. If the treatment does not act immedi- 
ately, it is advisable to vary the doses, sometimes 
reducing them and giving the remedy for a longer 
period. There is no doubt that this medication may 
render very great service in the treatment of cer- 
tain rheumatics, without exposing them to the least 
danger." Of course Leopold Levi looks at every 
disease from the standpoint of its relation to the 
thyroid gland — he has been called ''thyroid mad" 
— but the fact remains that he and his associate, 
Baron Henri de Rothschild, are successfully treat- 



134 THE INTERNAIv SECRETIONS 

ing scores of cases at their hospital with thyroid 
extract. 

The thymus is another gland which seems to be 
connected in some way with the joint manifesta- 
tions of rheumatism and several references have 
appeared in the literature in the last few years ex- 
tolHng the value of thymus extract in these chronic 
joint conditions. 

Naturally, it is not always possible to cure the 
disease — far be it from me to hint anything as defi- 
nite as this — but according to Nathan the first and 
most important beneficial change due to the thy- 
mus medication is a reduction in the pain present, 
and later, provided the case responds to the treat- 
ment, there is an increased mobility as w^ell as a 
general betterment of the nutrition and health. 

It is not yet possible to expain why thymus medi- 
cation does this and in what mysterious manner 
these results are brought about, but we know, at 
least, that in early life the thymus controls in a 
considerable degree the mineral metabolism, for 
one recalls that thymectomy causes a remarkable 
softening of the bones and an obvious disturbance 
of mineral metabolism. It may be, therefore, that 
there is a principle in thymus extract which favors 
the re-establishment of the disordered metabolism 
of calcium salts which is undoubtedly a factor in 
these rheumatic cases, and that the benefit is due 
solely to this. Suffice it to say that in the treat- 
ment of arthritis deformans Nathan recommends 



IN PRACTICAL MEDICINE 135 

15 to 30 grains of thymus substance three times a 
day given for weeks or months and some very en- 
couraging results have been reported. 

In conclusion let us remember the intimate rela- 
tion of the ductless glands to metabolism, the un- 
doubted connection between rheumatism and meta- 
bolic disturbances and, therefore, the possibilities 
of organotherapy as a meritorious adjunct in the 
treatment of certain forms of rheumatism. 



XII 

THE RELATION OF THE THYROID GLAND 
TO EPILEPSY 

THE study of the glands of internal secretion, 
now being taken up with avidity on all sides, bids 
fair to outrival many other phases of the study of 
medicine. Endocrinology has more to do with the 
really obscure and difficult problems of internal 
medicine than many have yet appreciated; and as 
our study becomes more thorough we are realizing 
the extremely intimate relation between the endo- 
crine organs and practically every phase of physio- 
logical activity. We are learning to appreciate as 
never before the importance over all of the body of 
the chemical effects produced by the hormones 
from these glands. 

To me the most interesting and recent work on 
so-called ''idiopathic epilepsy" (the only form of 
epilepsy referred to in this paper) is that of C. A. L. 
Reed, (1) of Cincinnati, whose several communi- 
cations have emphasized three important consid- 
erations: 1st, that intestinal stasis is almost with- 
out exception present in epilepsy; 2nd, that a prom- 
inent result of the associated toxemia is a varying 
degree of acidosis which produces a condition of 
edema of the brain to which a part, at least, of the 



Reprinted from The Lancet-Clinic (Cincinnati), July 29, 
1916. 

(136) 



IN PRACTICAL MEDICINE 137 

characteristic manifestations of epilepsy are due; 
and 3rd, that in operating in the manner of Lane 
on cases with pronounced intestinal stasis, a marked 
infiltration of the peritoneal and mesenteric glands 
is usually encountered, and that from these glands 
an organism, named by Reed the epileptococcus, 
frequently may be isolated. 

Though I do not question the findings of such an 
authority, I may be permitted to have an opinion 
as to the fundamental causation of the stasis, the 
acidosis, the edema and the glandular enlargement. 
For the moment I am not interested in the bacte- 
rial findings and the suggestion that we may event- 
ually work out a vaccine therapy for this disease. 

I believe that in every case of epilepsy there is a 
distinct endocrine element which is present and 
prominent much more frequently than has been ad- 
mitted in the literature on the subject. This will 
be discovered to be as early and constant a clinical 
manifestation as any others with which we are bet- 
ter acquainted at present. 

The principal organ of internal secretion in- 
volved is undoubtedly the thyroid gland, although 
others, notably the pituitary, gonads and parathy- 
roids, have been connected with the clinical find- 
ings of epilepsy. 

It may be well to reiterate some facts concerning 
the relation of the thyroid to the picture of intesti- 
nal stasis. The man to whom we are indebted for 
first directing our attention to the minor form of 



138 THE INTERNAL SECRETIONS 

thyroid insufficiency, Eugene Hertoghe, of Ant- 
werp, and who is still the leading student in this 
line, called particular attention to a syndrome 
identical with that so prominently brought to the 
fore by Sir Arbuthnot Lane, and did it nearly 
twenty years ago ! Quoting from a recent resume 
of his work (2) on "chronic benign thyroid insuffi- 
ciency" or "myxedeme fruste," we read: 

"The entire gastro-intestinal system reacts very 
strongly to the infiltration of its elements, whether 
muscular, nervous, secretory or mucous. Infiltra- 
tion of the muscular tissues induces peristaltic pa- 
resis, leading to retention of waste materials with 
consequent fermentation and constipation. In deli- 
cate subjects with weak abdominal walls this re- 
sults in ptosis of the viscera, notably of those or- 
gans which are most heavily loaded, namely, the 
stomach and large intestine. . . . Imperfect in- 
testinal drainage gives rise to intestinal toxemia, 
which reacts upon the already enfeebled thyroid 
and intensifies the prevailing conditions of inade- 
quacy. As a matter of fact, many of the symptoms 
attributed by Lane to chronic intestinal stasis are 
identical with those which, since 1899, I have in- 
cluded in the symptom-complex of benign chronic 
subthyroidism. These are hypothermia, uncon- 
trollable headache, rheumatoid pain and neuralgia, 
mental depression, dyspnea, asthmatic attacks, pre- 
mature grayness and baldness, dental caries, chole- 
lithiasis and brownish pigmentation of the skin." 



IN PRACTICAL MEDICINE 139 

It should not be difficult to demonstrate a fur- 
ther relation between the thyroid and epilepsy. The 
insignificant, but none the less important, signs of 
the slighter form of dysthyroidism are very com- 
monly found in epilepsy, occasionally one or two 
of them being very well marked, or again, several 
of them together but not especially definite or ob- 
vious. This is the usual reason that the thyroid 
element is overlooked; but when one is careful, 
some of these signs will be found. The permanent 
or transitory edema or infiltration of various tis- 
sues results in such widely differing symptoms as 
nasal obstruction,* changes in the voice, headache, 
migraine, a dry, rough skin, thinning of the hair 
and especially the outer third of the eyebrows, cold- 
ness of the extremities, abnormal chilliness, dull- 
ness and backwardness, menstrual disorders, etc. 

These symptoms, together with those mentioned 
in the above quotation from Hertoghe, include a 
majority of the clinical findings of hypothyroidism. 
While it is not possible here to go into the whole 
subject, we must mention the frequency of dys- 
crasias in other ductless glands in epileptics, espe- 
cially of the gonads, for it is well established that 
there is a distinct connection between puberty and 



♦There are numerous incidents on record in nose and throat 
literature which indicate that when deflected nasal septa and 
other obstructive conditions of the nose and throat have been 
surgically removed, there has been a coincident benefit as regards 
the number and severity of the epileptic seizures. Many times 
these obstructions are not altogether organic, and when the 
mucosal infiltration is associated with thyroid insufliciency and 
Is removed by thyroid therapy, the results are equally good. 



140 THE INTERNAL SECRETIONS 

the menses, and epilepsy. It is common to find that 
some menstrual irregularity, or even what appears 
to be the normal menstruation, seems a signal for 
the onset of a seizure. Hundreds of cases have been 
seen in which a decided ovarian element was pres- 
ent, and, in most of these, I am sure that there has 
been an equally prominent thyroid disturbance 
which many times was responsible, in part at least, 
for the epileptic and the menstrual disturbances. 

In passing, I might mention an interesting and 
somewhat confirmatory report by Weeks and Ren- 
ner (3) on a case of Raynaud's disease associated 
with epilepsy. Within the past year, no less an 
authority than Oliver T. Osborne, (4) of Yale, has 
shown that the several vasomotor disorders, of 
which Raynaud's symmetrical gangrene is the ex- 
treme type and chilblains is a lesser type, are al- 
ways associated with thyroid disorder, although 
other ductless glands may be simultaneously in- 
volved."^ According to Osborne, thyroid therapy, 
judiciously employed, causes improvement in most 
cases of Raynaud's disease and some cases are 
actually cured. 

There is something more than incidental in the 
relation of the alimentary conditions in epilepsy to 



♦Let me mention here, parenthetically, that it is practically- 
impossible to have a disorder of the endocrine glands involving 
a single gland of internal secretion. Their hormonic relation is 
so intimate (or as McCord has so well expressed it, the glands 
of internal secretion constitute an "interlocking directorate which 
controls the body"), that uniglandular disorder invariably means 
a pluriglandular complex. 



IN PRACTICAL MEDICINE 141 

those we may expect in chronic hypothyroidism. In 
epilepsy it has long been recognized that the ten- 
dency to constipation invariably present (despite 
the fact that we are often told that "the bowels 
move quite normally") complicates the disease by 
aggravating the intensity and frequency of the 
seizures. It is now universally known that one 
must always give special care to the bowels, irre- 
spective of seeming normality, and also cut down 
the protein intake, especially the amount of meat. 
In hypothyroidism, also, a similar form of consti- 
pation is the rule. Leopold Levi, (5) the greatest 
French authority on thyroid dyscrasias, lays em- 
phasis on his opinion that constipation of thyroid 
origin is frequent and, perhaps, is the most frequent 
form of constipation. 

Both epilepsy and thyroid disorders very com- 
monly have an hereditary predisposition underly- 
ing them. Cretinism, of course, is not an acquired 
disease, and the hereditary tendency to thyroid in- 
stability is one of the easiest to trace back of all of 
the factors present. I need only remind you of the 
frequency of thyroid instability in the children of 
parents, and especially mothers, with irregularities 
of the ductless glands, or mention the well-known 
fact that an undue strain upon the thyroid appa- 
ratus prior to or during pregnancy is the most 
usual basic cause for many of the varying degrees 
of thyroid inadequacy that we discover almost ev- 
ery day if we look keenly for them. 



142 THE INTERNAL SECRETIONS 

Thorn* studied 157 cases of epilepsy quite re- 
cently and found that no less than 126 showed a 
direct hereditary connection — either a parent or a 
grandparent had the disease. In thirty-eight per 
cent, of the series studied, epilepsy was associated 
with alcoholism — one of the commonest causes of 
acquired or transmitted functional or organic en- 
docrine disorders. Mental disorders were pres- 
ent in twenty-seven per cent, of the parents of these 
cases and feeble-mindedness in more than ten per 
cent. We need not more than mention in passing 
that one of the most frequent causes of feeble- 
mindedness is thyroid disorder, and that insanity 
has been connected by numerous writers with dis- 
orders of one or more of the ductless glands, usu- 
ally the thyroid or the ovaries, as often as with any 
single condition. Still further, I am confident that 
some day it will be better understood that the two 
most prolific causes of insanity — syphilis and alco- 
holism — bring it about by their insidious disorgan- 
ization of the work of the glands of internal secre- 
tion, more than in any other manner. 

There are various communications in the French 
medical literature, to which reference should be 
made. Gauthier (6) has collated many, and sup- 
plements them with several personal case reports. 
He finds that thyroid therapy is a helpful measure 
in epilepsy, especially where other evidences of thy- 



*Figures quoted from editorial in Ellingwood's Therapeu- 
tist, 103 (1916). 



IN PRACTICAL MEDICINE 143 

roid insufficiency are present. It may be well to 
translate a few lines from his book: 

"Epilepsy is considered by a large number of 
physicians and neurologists to be an intoxication, 
or a general disorder of metabolism. There is also 
a possible connection in certain cases with the work 
of the thyro-parathyroid combination. The asso- 
ciation of epilepsy with myxedematous idiocy, 
cretinism and even Basedow's disease is well 
known. But there are other evidences. Many cases 
of simple goiter become epileptic and goiterous 
mothers give birth to epileptic children (Rapp, 
Jeandelize, Parhon, Goldstein, Hertoghe, etc.). 
Claude and Schmiergeld, (7) in a study of seven- 
teen cases of epilepsy from the endocrine point of 
view, have found in every case alterations in the 
thyroid gland and in twelve of these the structure 
of the gland was completely altered with areas of 
sclerosis and limited zones of compensatory hyper- 
trophy of the glandular tissue. . . . Parhon (8) 
examined the thyroid in twelve epileptics. He 
found it smaller than usual and showing frequent 
and variable histologic changes, and, interestingly 
enough, the iodin content was very often in- 
creased." 

The cerebral edema which Reed and Martin 
Fischer of Cincinnati are now convinced is a result 
of the toxic acidosis, is just as likely to be of thy- 
roid as of intestinal origin, for not only may the 
acidosis or systemic hypoalkalinity result from the 



144 THE INTERNAL SECRETIONS 

loss of the full effective hormonic service of the thy- 
roid, but the essential infiltration,* w^hich is the 
typical pathognomonic feature of hypothyroidism 
affects all the tissues of the body, for the thyroid 
exerts a cellular influence w^hich is not limited to 
any organ or set of organs, hence, not only the 
brain, but also the peritoneal and mesenteric glands 
may be infiltrated as noted by Reed and mentioned 
in the beginning of this paper. In this connection 
it may be w^ell to state that Hertoghe (9) has de- 
scribed a form of coma of thyroid origin in vvrhich 
one of the constant findings on autopsy was an in- 
filtrative edema of the brain. 

A certain well-defined fact, first set forth by Her- 
toghe and later by Leopold Levi, enables us to give 
a final emphatic demonstration that the position 
held regarding the importance of the thyroid ele- 
ment in epilepsy is not untenable. Benefit from 
thyroid therapy can not be expected in the numer- 
ous conditions for which it is given unless there is 
a definite need for the chemical substances or hor- 



*The most marked result of the loss of the thyroid hormone 
is a condition of cellular inactivity and mal-elimination. This 
results in a peculiar form of infiltration which may affect any 
cells that are under the influence of this gland. This means 
practically all forms of tissue. This infiltration is best recog- 
nized in the puffy, dough-like skin of myxedema, and while it 
may not be so marked, it is the principal cause of the majority 
of the manifestations of thyroid insufficiency. One can readily 
understand that the obesity, stiffness of the muscles, ligaments 
and joints, intestinal sluggishness, and in fact, disturbed cell 
activities in general, including the brain, nerves and tissues gen- 
erally, may be thus referred to a more or less well-marked 
metabolic inactivity which follows the loss of the essential hor- 
mone stimuli which the thyroid sends to every part of the body. 



IN PRACTICAL MEDICINE 145 

mones thus administered. In Levi's words (10): 
"When the results of treatment with thyroid ex- 
tract are immediate, continued, constant or pro- 
nounced, they may be regarded as a diagnostic fac- 
tor." Hertoghe tells us the same thing in other 
words: ''If certain patients are carefully exam- 
ined, they will be found to show symptoms of gen- 
eral thyroid insufficiency, and this is invariably the 
case with those who derive benefit from thyroid 
medication." 

There are not a few reports from which we may 
gather that empirical thyroid therapy has exerted 
some beneficial effect in epilepsy. I have noticed 
this a number of times myself, though I should not 
want to imply that the benefit was solely due to 
the thyroid medication. Many of us, perhaps, have 
given this remedy in anticipation of a possible bene- 
fit just as we have come to expect, somewhat un- 
scientifically it is true, that thyroid extract may 
help a host of widely differing conditions. These 
scattered results are among the best reasons for ap- 
plying the etiologic, diagnostic and therapeutic 
principle which I am discussing. When applied 
systematically in the routine treatment of epilepsy 
in which one can find clinical evidence of hypothy- 
roidism, accompanied, of course, with such other 
curative and symptomatic treatment as the exi- 
gencies of each case demands, the prognostic pros- 
pects should be considerably better. 

With these opinions in mind, we are justified in 



146 THE INTERNAL SECRETIONS 

drawing some conclusions which seem to have a 
reasonable bearing on the subject under discussion: 

1. That thyroid insufficiency is likely to be a fre- 
quent underlying factor in the etiology of epilepsy 
for several reasons: (a) It favors toxemia; (b) it 
produces cellular infiltration and edema, which may 
affect the brain in the manner described by Her- 
toghe, Reed and others, and (c) it usually causes 
other symptoms in epilepsy which have been defi- 
nitely attributed to hypothyroidism. 

2. Hence the study of epilepsy from the stand- 
point of the glands of internal secretion is rational 
and worth while. 

3. Thyroid therapy is a rational therapeutic ad- 
junct in the treatment of epilepsy accompanied by 
other signs of hypothyroidism. 

4. Favorable results from the use of thyroid ex- 
tract in epilepsy should be considered as a confirma- 
tion of these conclusions; and an incentive to fur- 
ther clinical study in this direction. 

In closing I do not want to leave the impression 
that a few weeks of thyroid therapy will cure epi- 
lepsy. Rather do I wish to emphasize that the thy- 
roid gland, because of its intimacy with detoxica- 
tion and metabolism in general, deserves to be con- 
sidered in the investigation of every case of epi- 
lepsy; and where one finds other evidences of 
waning thyroid sufficiency, thyroid therapy may be 
instituted in conjunction with other rational treat- 
ment, and a better percentage of results be attained. 



IN PRACTICAL MEDICINE 147 

REFERENCES 

1. C. A. L. Reed: Journal Am. Med. Assn., 66, 336 
(1916) ; Journal Am. Med. Assn., 64, 1,047 (1915) ; Lancet- 
Clinic, 112, 102 (1914). 

2. E. Hertoghe: Practitioner, 94, 24 (1915). 

3. D. F. Weeks and D. S. Renner: Jour. Am. Med. 
Assn., 66, 651 (1916). 

4. O. T. Osborne: Am. Jour. Med. Sci., 150, 157 
(1915) ; see also Amer. Med., 10, 784 (1915). 

5. L. Levi : *'La Petite Insuffisance Thyroidienne et 
son Traitement," Paris, 1913, p. 91. 

6. G. Gauthier: "L'Opotherapie Thyroidienne," 358. 
Paris, 1913. 

7. H. Claude and Schmiergeld: Les Glandes a Secre- 
tions Internes chez les Epileptiques, L'Encephale, Janu- 
ary, 1909. 

8. Parhon et al : Rev. Neurologique, January, 1908. 

9. E. Hertoghe: Du Coma M)rxedemateux. Bull 
Acad. Roy. de Med. de Belg., February 25, 1911. 

10. Leopold Levi: Practitioner, 94, 199, 1915. 



XIII 

THE DEFECTIVE CHILD FROM THE 

STANDPOINT OF THE INTERNAL 

SECRETIONS 

DEFECTIVE children, or "children requiring 
special attention" as a colleague appreciative of the 
sensibilities of the parents calls them, are practic- 
ally without exception endocrine cases. 

There are several comprehensive classifications 
of defectives; and the methods of measuring their 
physical and mental capacity, or lack of it, enables 
us to place a given case in the same class as others 
affected in a similar degree. This, however, does 
not indicate the etiologic factors influencing the 
child and, hence, the proper treatment. 

It is true that children handicapped with hered- 
itary syphilis, epilepsy or any transmitted disease 
or disease tendency, more often are considered as 
syphilitic or epileptic rather than as suffering from 
dyscrinism. Nevertheless the fact remains that in 
all such cases the endocrine element is both pres- 
ent and prominent irrespective of the simplicity or 
complexity of the trouble and its cause. 

With our present knowledge we may safely say 
that the treatment of defective children offers bet- 
ter prospects of success than ever before. Of course 



Reprinted from the Southern California Practitioner (Los 
Angeles) July, 1917. 

(148) 



IN PRACTICAL MEDICINE 149 

what is known as feeble-mindedness or amentia 
may be more than a mere ''deficiency," for the cere- 
bral development may be imperfect and here there 
is little or no hope for a successful outcome. 

In the past few years considerable interest has 
been aroused in the relation of endocrinology and 
the study of defective children; and it is surprising 
how many of the stigmata which cause us to place 
children in this category are connected with abnor- 
mal endocrine function and, too, how frequently on 
investigating their antecedents we uncover a more 
or less well marked endocrine disorder in the 
parents or grandparents which properly may be re- 
garded as a part of the cause of these unfortunate 
conditions in their offspring. 

The hereditary phase of the relation of dyscrin- 
ism to defectives will be referred to again later as 
it seems to be a hopeful phase of a very hopeless 
subject. 

It will be my endeavor here to lend emphasis to 
the importance of considering this subject from 
the chemical rather than the physical standpoint, 
and to secure more attention by readers to the 
study of the ductless glandular manifestations, ob- 
vious or insidious, in defective children. 

There are almost as many forms of develop- 
mental anomalies in children as there are glands of 
internal secretion. Chief among them all are those 
relating to dysthyroidism. The cretin, well known 
to be typical of a large class of deficients, is an 



150 THE INTERNAL SECRETIONS 

endocrine case pure and simple, the syndrome be- 
ing definitely traced to deficient thyroid activity 
and, fortunately, being decidedly benefited by sub- 
stitution therapy or the administration of the miss- 
ing chemical substances. In fact a large part of 
our first knowledge of the clinical importance of 
dysthyroidism resulted from the studies of George 
Murray, Sir William Gull and Theodore Kocher 
some twenty-five years ago upon individuals who 
were all in one way or another mentally and phys- 
ically defective. 

The literature upon the retarded, backward or 
deficient child recently has begun to contain ref- 
erences to the syndrome ''hypoplasia" and accord- 
ing to Noble (1) the hypoplastic individual is one 
whose nutrition and development is below par, the 
condition being congenital or acquired during in- 
fancy or early childhood. There are varying de- 
grees of hypoplasia reaching from backwardness 
which is not appreciated until the child has been 
some time in school, to the serious organic dyscrin- 
ism which is sometimes called infantilism and 
sometimes mal-development. 

It is difficult to say how much of the symptom- 
atology of this condition of hypoplasia may be re- 
ferred to the thyroid gland. Much of it at least 
is of thyroid origin and Hertoghe (2) refers to it 
frequently in his writings and uses the term "thy- 
roid inanition" as indicating a condition of slow 
starvation and inactivity without particularly ob- 



IN PRACTICAL MEDICINE 151 

vious changes in contour or weight. Function, 
however, is much below par and it is but a short 
step from the unappreciated ''forme fruste" of thy- 
roid insufficiency to the myxedematous idiocy de- 
scribed by Brissaud, or the Lorain type of infantil- 
ism, in the former of which mental development 
seems to be more definitely affected while in the 
latter the mind is clear and capable and physical 
development is deficient. 

Hypoplasia in children according to E. B. Mc- 
Cready of Pittsburgh, who is a close and intelligent 
student of this subject, properly may include the 
backward child 'Svho is retarded in his develop- 
ment by reason of some condition either inherent 
in the child himself, which can either be removed 
or counteracted, or who is subject to some physical 
defect or environmental condition, the removal of 
which will allow him to progress in a normal man- 
ner under favorable opportunities.'' (3) 

From the standpoint of this author, with whom 
I am heartily in accord, the hypoplastic child is not 
necessarily a sufferer from an unchangeable de- 
velopmental complex. The stimuli to growth and 
development have not been sufficiently strong and 
these necessary manifestations are at a standstill 
or below par. Fortunately this class constitutes a 
large proportion of the so-called ''backward chil- 
dren" and from a clinical standpoint the prognosis 
has been radically changed for the better since the 
advent of scientific endocrinology and a better ap- 



152 THE INTERNAL SECRETIONS 

preciation of the possibilities of substitution ther- 
apy. 

The hypoplastic individual is suffering from an 
arrested development. All function is at half-speed 
or even slower and among the early symptoms 
enumerated by McCready (4) are: Delay in the 
power of walking and talking, late closing of the 
fontanelles, irregular dentition, though progress 
in these respects may be entirely normal and even 
more rapid than normal for the precocious child 
is often an hypoplastic one. Additional early signs 
are nocturnal enuresis, the so-called scaphoid scap- 
ula, a tendency to lymphatism with adenoids and 
hypertrophied tonsils, and pronounced malnutri- 
tion. 

Leonard Williams (5) has brought together 
enough clinical and therapeutic evidence to estab- 
lish the fact that enuresis in the hypoplastic child 
is largely a result of thyroid insufficiency, which is 
so commonly present, and the successful admin- 
istration of thyroid extract in these cases tends to 
bear out this contention. Incidentally Williams 
believes that adenoids and enlarged tonsils repre- 
sent a compensatory action of the body, tending 
to counterbalance the thyroid insufficiency. 

Graves (6) finds the scaphoid scapula so com- 
mon in these cases that in a report of 47 children 
who were behind in their grades, all were under 
size and showed various anomalies in development, 
58 per cent, were mouth breathers, 17 per cent. 



IN PRACTICAL MEDICINE 153 

were subject to enuresis and 85 per cent, showed 
the scaphoid scapula. Another fairly constant 
symptom, according to McCready, is the high- 
arched palate which is presumed to be produced by 
the yielding of the palatine bones owing to their 
relative deficiency in calcium. Enlarged tonsils 
and adenoids, while common enough, are more 
likely to occur in hypoplastic children and accord- 
ing to Noble (1) this pathological condition of cell 
hypoplasia explains the reason for a large group 
of debilitated women and also all the children who 
are not vigorous and who have adenoids and dis- 
eased tonsils and who become mouth breathers. 

It is not possible within the limits of this brief 
communication to mention a tithe of the state- 
ments in the last ten or fifteen years regarding the 
endocrine basis of developmental disorders in chil- 
dren, but if the students of these ''children requir- 
ing special attention" will look carefully for the 
functional accompaniments of thyroid insufH- 
ciency* (7) they will be found in a large proportion 
of the cases. 

Probably the next most important gland that 
deserves study in this class of cases is the thymus, 
for thymus enlargement or in older children the 
persistent thymus, is found to be very com- 
monly connected with disorders of this character. 



*To avoid repetition the reader is asked to read Chapter IV 
in this connection and especially the symptomatology of hypo- 
thyroidism as outlined on page 38. 



154 THE INTERNAL SECRETIONS 

just as a premature atrophy or absence of the thy- 
mus also may be found. Hard and fast statements 
can not yet be made as to the real function of this 
gland. Some deny its internal secretory powers 
and call it merely lymphoid tissue. Not all are 
unanimous about the relations of this gland, but 
from a clinical standpoint, I am certain that the 
thymus is involved in many cases of this character 
for I have personally demonstrated an enlarged 
thymus in a number of children that have come to 
me for diagnosis or treatment and follovi^ing a flu- 
oroscopic examination I have had these children 
irradiated and later on re-examination have dis- 
covered a considerable reduction in the thymic 
shadov^ w^hich v^as accompanied by benefit to the 
symptom complex under treatment (though of 
course I admit that this procedure just mentioned 
was but a part of the treatment). 

There is no question about the defectiveness of 
children suffering from the well-defined status 
thymico-lymphaticus, though mentality may be 
normal. In such cases an early diagnosis may be 
facilitated by a differential blood count in which 
the lymphocytes will be found to be greatly in- 
creased (100 per cent, or more). There will be 
hyperplasia of various groups of lymph glands as 
well as the tonsils and spleen and the skin will have 
a pale, badly nourished appearance and occasion- 
ally there will be an associated mal-development 
of the genitalia. 



IN PRACTICAL MEDICINE 155 

Thymus hyperplasia in children is usually ac- 
companied by the "hypoplastic state" referred to 
before. The increased cellular growth of the thy- 
mus and other lymph structures is modifying the 
chemistry of the body in such a way that the defi- 
ciencies of hypoplasia are permitted to show them- 
selves. These individuals are of the flabby, semi- 
obese type and practically always have other evi- 
dences of developmental dystrophy. Occasionally 
in addition to the osseous changes already men- 
tioned (high arched palate and scaphoid scapula) 
the bony development is modified seriously, the 
epiphyses are late in joining and rickets may be 
present.* 

On the other hand, Bourneville has shown from 
a large series of autopsy findings that over 70 per 
cent, of mentally defective and epileptic children 
have no thymus at all. This may seem to be contra- 
dictory but it is none the less suggestive as it di- 
rects attention to the thymus as a regulator of the 
chemistry, and whether deficient or excessively 
active, it is a factor deserving of our study. 

While it is granted that our knowledge of the 
thymus gland is none too definite as yet, we are 
safe in assuming it to be an important factor in 
defective children, and initiating a careful physical 
examination for the gland itself and a search for 



*A number of writers indicate a clinical connection between 
thymus disorder and rickets; and the subject is considered from 
the standpoint of treatment in the prize article which consti- 
tutes Chapter XVIII. 



156 THE INTERNAL SECRETIONS 

evidences of dysthymism. If this search is unre- 
munerative it is a great advantage to me to have 
ruled out the HkeHhood of thymic involvement for 
not infrequently it is present and ignored alto- 
gether with obvious detriment to the success of the 
best of treatment. 

Still another gland is prominently identified with 
developmental disorders in children. The hypo- 
physis or pituitary has much to do with the chem- 
ical control of development and while it may not 
be so important as the thyroid it is more important 
than some have thought. Quite the most important 
recent step in the development of our knowledge 
of the ductless glands is the discovery by T. Brails- 
ford Robertson of the University of California of 
the active principle of the pituitary gland proper, 
tethelin, and its growth-controlling function. (8) 
It is entirely possible that in tethelin we may find 
a most useful means of stimulating deficient 
growth though to date the use of this principle has 
been largely limited to the laboratory. So far I 
have used the desiccated anterior lobe of the pitu- 
itary in fourteen cases with advantage in enough 
to establish my confidence in this form of treat- 
ment. Suffice it to say that many deficiencies in 
children have a pronounced pituitary origin and it 
is a routine in my work to study all such children 
from a pituitary standpoint. Radiographs of the 
sella turcica are made, and quite often I have found 
obvious changes in the shape and size of the pitu- 



IN PRACTICAL MEDICINE 157 

itary fossa. An interesting case is already men- 
tioned elsewhere in this book* and while pituitary 
feeding is being practiced more frequently, too 
often I am finding that this has been done in cases 
coming to me for consultation, without any ac- 
curate reason therefor and naturally without good 
results. I have in mind a case of developmental 
dystrophy that had been treated for many months 
first with thyroid and then with pituitary and then 
with both, without the slightest beneficial results. 
The case was none the less one in which gland 
feeding was in order, but this was not successful 
until given with reason and accompanied by such 
adjuvant procedures as needed to be carried out 
simultaneously. In other words, it is bad policy 
to treat symptoms instead of patients, for not in- 
frequently such treatment is unsuccessful and the 
interest of physician and parent in this is lost when 
in reality it is the only hopeful thing. 

Pituitary infantilism is very completely studied 
and illustrated by Gushing and his monograph* is 
the most comprehensive piece of literature on the 
subject extant. 

The adrenals likewise may be involved and ad- 
renal sensitiveness is not uncommon in defective 
children. Slight psychic or emotional stimuli make 
a very great impression on them. They fatigue 



*See Chapter V, page 58. 

♦The Pituitary Body and Its Disorders, by Harvey Gushing, 
J. B. Lippincott Co., 1912, Philadelphia. 



158 THE INTERNAL SECRETIONS 

easily and the cardio-vascular tone is low. I have 
noted a number of times a peculiar bluish mottling 
of the skin, especially of the lower parts of the 
body and a tendency to dermographia, which I 
have laid to some adrenal element in the pluri- 
glandular disturbance. These circulatory-cutane- 
ous manifestations may not be of great diagnostic 
significance per se, but they are of value as indi- 
cators of a prospective dyscrinism and a means of 
stimulating further study of the endocrine func- 
tions. 

Already considerable emphasis has been laid 
upon the importance of pluriglandular dystrophies 
and I may say that I have never seen a defective 
child in which there was a pure monoglandular 
disorder, and I do not believe there ever has been 
such a case. The reasons for this have already been 
quite fully discussed elsewhere in this book and the 
obvious therapeutic indication is to be sure that 
our treatment is comprehensive. 

McCready* in his work along this line has de- 
vised a combination of glandular extracts which 
he has had prepared for him by Messrs. Burroughs, 



*I think it is only proper to give much credit to Dr. Mc- 
Cready for the aggressive and intensive way in which he has 
studied what he chooses to call "pedology." He has unusual 
facilities in the Children's Courts at Pittsburgh and also his 
institution "Wildwood Hall" offers ideal facilities for the suit- 
able care of children requiring special attention. The success- 
ful treatment of this class of cases involves not merely glandu- 
lar feeding but intimate hygienic and dietetic control, special 
education and an ideal environment; and it is almost impossible 
to secure these at home or in most institutions in which such 
cases are handled by the State. 



IN PRACTICAL MEDICINE 159 

Wellcome & Co. This is now obtainable in trade 
under the name "Tabloid Mixed Glands" and to 
my mind this is a much more satisfactory treat- 
ment than the single extracts which we have been 
wont to use in the past, and it has the advantage 
of enabling one to stimulate the endocrine system 
as a whole rather than a part of it; and where 
necessary, by adding additional amounts of such 
other extracts as may seem to be indicated, spe- 
cial homo-stimulation may be brought about. 

It would not be proper to dismiss the subject 
without considering a phase of it which is deserv- 
ing of much more concerted study and action. Not 
a little concentrated attention has been directed at 
the huge task before the medical profession of pre- 
venting as far as possible the dire results of mental 
and physical defects and diminishing the extent of 
this most pitiful of all phases of social medicine. 

Perhaps the most reasonable and practically in- 
teresting communication on this subject is the ad- 
dress by Sajous (9) in which he makes a plea for 
co-operation along a line which is altogether new. 
Sajous brings sufficient evidence to show that 
glandular insufficiencies of a minor character in 
mothers are likely to be impressed upon their un- 
born offspring and the obvious thing to do in cases 
of this character is to be sure that these insuffi- 
ciencies are minimized at the time when this treat- 
ment will offer the greatest prospects of results. In 
other words, if a mother is suffering from thvroid 



160 THE INTERNAL SECRETIONS 

insufficiency it is likely that her child will have 
leanings in the same direction and thyroid feeding 
is in order during pregnancy. I have personally 
discovered in scores of cases a very clear relation 
between ductless glandular disturbances in the 
mother and her offspring. In fact it is almost the 
rule to find that the woman with a goiter transmits 
a tendency to goiter to her daughter and when pa- 
tients come for treatment the history will show 
almost always a hereditary basis for troubles of 
this character. 

I can do no better than to select a few weighty 
sentences from Doctor Sajous' address, as by re- 
printing them a greater appreciation of this sub- 
ject may be stimulated: 

''Any disease capable of injuring the ductless 
glands sufficiently to inhibit their functional activ- 
ity impairs correspondingly the development and 
functional activity of the brain, by reducing the 
supply of secretions this organ requires to carry 
on these physiological processes." 

"The main underlying cause of defective men- 
tality in both parent and offspring is inherited de- 
ficient activity of the ductless glands." 

"We should start a campaign having in view the 
salvation of these unfortunate infants by supply- 
ing, through the intermediary of their defective 
mothers, and, after birth, through their food, the 
secretions they lack to complete their develop- 
ment." 



IN PRACTICAL MEDICINE 161 

"In the majority of functional cases of feeble- 
minded and backward children met in current 
practice, the predominating pathogenic factor is 
hypothyroidism, though deficiency of other inter- 
nal secretions is also discernible in most instances." 

"On the whole, the intimate relationship between 
the ductless glands and everything that concerns 
reproduction, the greater relative size of these or- 
gans in the product of conception, and the teach- 
ings of practical experience in organotherapy, all 
tend to indicate that whenever the father or mother 
is a mental defective, or both parents show any 
sign of deficient activity of one or more ductless 
glands, or are mental defectives, organotherapy 
should be instituted as soon as pregnancy is recog- 
nized." 

"The mental and physical status of all pregnant 
women as regards the functional efficiency of their 
ductless glands, which may be determined by the 
stigmata of deficiency of these organs, should in- 
variably be established. If found deficient, organo- 
therapy should be used to protect them against 
renal disorders and convulsions through toxemia, 
and also their offspring against imperfect develop- 
ment and mental deficiency." 

In closing I feel to add that the foregoing state- 
ments are deserving of the closest attention, and 
that the principle so clearly enunciated applies to 
all deficients or defectives and not merely to those 
in which the mental element predominates. 



162 THE INTERNAL SECRETIONS 

REFERENCES 

1. Chas. P. Noble, Hereditary Hypoplasia in Man, 
Due to Degeneracy. Jour. A. M. A., Feb. 3, 1909. 

2. E. Hertoghe, Thyroid Insufficiency. Practitioner 
(Lond.), Jan., 1915. 

3. E. Bosworth McCready, The Care of the Excep- 
tional Child. Arch. Pediatrics (N. Y.), June, 1911. 

4. Ibid, Retarded Mental Development in Children, 
Internat. Clin. (Phila.), 1913, Vol. I. 

5. Leonard Williams, Clinical Lecture before Medi- 
cal Graduate College, London. Polyclinic (Lon.), Jan., 1909. 

6. W. W. Graves, The Scaphoid Scapula, Medical 
Record (N. Y.), May 21, 1910. 

7. Henry R. Harrov^er, The Inconspicuous, Every- 
day Forms of Thyroid Insufficiency. California State 
Journal of Medicine (San Francisco), May, 1916. 

8. T. Brailsford Robertson, Recent Investigations of 
the Influence of the Anterior Lobe of the Pituitary Body, 
and on the Properties of the Growth-Controlling Constitu- 
ent Tethelin. Endocrinology (Los Angeles), Jan., 1917. 

9. Chas. E. deM. Sajous, Our Duty to Mental De- 
fectives of the Present Generation. New York Med. Jour., 
April 1, 1916. 



XIV 

ORGANOTHERAPY IN CHRONIC DISEASE 

WITH SPECIAL REFERENCE TO ITS 

POSSIBILITIES IN CANCER 

THE treatment of chronic disease, at best too 
often a difficult and unsatisfactory matter, has 
been considered by so many physicians so many 
times that further reference to the subject may 
seem to be almost out of place, for already there 
is an overwhelming number of papers and many 
books concerned with the advantages of all forms 
of treatment of chronic disease, from the surgical 
removal of presumably offending organs to the 
Emanuel Movement, and including other more or 
less useful methods such as hydrotherapy, electro- 
therapy, psychotherapy, serotherapy, autotherapy, 
and, most recent of all, the intestinal short circuit 
as suggested by Sir Arbuthnot Lane. 

The mere fact that disease has been present for 
more than the proverbial forty days and that a 
good percentage of chronic invalids perambulate 
from one doctor's office to another, as well as the 
suggestion already made that many widely differ- 
ing forms of treatment are advanced more or less 
enthusiastically from time to time, seem to be con- 



An address read by invitation before the Medical Associa- 
tion of the Greater City of New York, February 15, 1915, and 
published in the New York Medical Record July 3, 1915. (Copy- 
right, William Wood & Company.) 

(163) 



164 THE INTERNAL SECRETIONS 

vincing evidence that the treatment of chronic dis- 
ease is still an unsolved problem and hence worthy 
of persistent study. 

This evening it is proposed to consider another 
fairly well known phase of therapeutics and to urge 
its more frequent application to the indefinite and 
chronic disorders, many of which have not the 
dignity of a name and others of which are classed, 
rightly or wrongly, under the name of the principal 
symptoms, chief among these being neurasthenia. 
It does not seem advisable, at this stage of prog- 
ress, to make any hard and fast statements, hence 
all that may be said here to-night will be purely 
suggestive, the prospective value of such proced- 
ures as may be mentioned being left to the judg- 
ment of those who, being convinced of the reason- 
able basis outlined, may be sufficiently interested 
to put them to the test. 

There seem to be fashions in medical matters 
just as there are in dress or art. If I am not much 
mistaken it is beginning to be the fashion to study 
and write about the internal secretions. A number 
of books have appeared on this subject. I even 
plead guilty to having written one on the thera- 
peutics of the internal secretions. There are, with- 
out the least exaggeration, thousands of papers on 
the various phases of this fascinating subject pub- 
lished in practically every quarter, chiefly however 
in French, Russian, and Italian. 

All this is as it should be, for from all sides come 



IN PRACTICAL MEDICINE 165 

words of commendation and evidences of profound 
interest, and every interested physician that I have 
had the pleasure of meeting in half a dozen differ- 
ent countries has manifested an unwonted enthusi- 
asm in his investigation of this subject — it breeds 
enthusiasm, for so often we stumble across the 
most startlingly wonderful things which when 
they are first published abroad are usually greeted 
with the smile of scorn, just as were Roentgen's 
remarkable rays, or Marconi's equally amazing dis- 
covery, or Alexander Graham Bell's wonderful in- 
vention, by which all of us have profited so much. 
Sir William Osier told me only a short time ago 
when I visited him at Oxford that surgery had 
been having its innings for the past ten years or 
more and it was time for medicine to have its turn 
and probably the "bat" would be the internal se- 
cretions of the ductless glands. For instance, what 
surgical discovery excels in its scope and wonder 
the many-sided usefulness of pituitary extract? 

In these days of advance in physiological and 
pathological research we have gradually accumu- 
lated a fair knowledge of the series of organs which 
were until recently almost entirely unknown. We 
have learned that the ductless glands or endocrin- 
ous organs exercise an intimate control over met- 
abolism and the celluar activities, that this is in 
all probability brought about by definite chemical 
substances produced in these organs and conveyed 
from them to others by means of the blood and 



166 THE INTERNAL SECRETIONS 

lymph — the "hormones," so named by Starling in 
1902 — and, best of all, that it is possible to secure 
from animal glands certain active hormone-bear- 
ing substances in a more or less pure state which 
are available in the treatment of the disease. 

We cannot stop to consider the occasional state- 
ments to the effect that organotherapy is a fad, or 
that it is still in its infancy and hence not worthy 
of more than passing consideration, and that much 
more work will have to be done before the subject 
reaches a really practical stage. Those who mani- 
fest such sentiments invariably make their state- 
ments without deliberation and due consideration 
of the facts. None can deny that certain of the 
ductless glands produce extremely active principles 
which have an equally active influence in the con- 
trol of normal as well as morbid phenomena. We 
have only to recall the influence of thyroid extract 
in myxedema, adrenalin in local hemorrhage, or 
pituitary extract in labor to realize that there are 
sufficient inducements to delve more deeply into 
the study of the extracts of these organs, as well 
as of others known to be concerned in the main- 
tenance of what is now termed "the hormone bal- 
ance.'' 

This factor deserves much more consideration 
than it is possible to give it this evening, for the 
delicate balance brought about by the interrelation 
of the internal secretions is concerned in the main- 
tenance of essential health none the less than in 



IN PRACTICAL MEDICINE 167 

the production of deviations therefrom. I am go- 
ing to propound what I beheve to be an axiom — it 
is impossible for an individual to manifest the re- 
sults of chronic disease v^ithout a corresponding 
disturbance in some or all of these hormone-pro- 
ducing organs. Further than that, I believe that 
many of these intractable symptoms-complex, to 
which it is sometimes so difficult to give a suitable 
name, are often aggravated by a disturbance in 
what has been termed the "altruistic function" of 
the cell. I will explain: Campbell considers that 
cell activity is properly divided into the egoistic 
and the altruistic ceil functions. The former con- 
sists in the maintenance of individual cell activity, 
while the latter concerns the supply to the organ- 
ism as a whole of certain services, probably 
brought about by the hormones, such as are ex- 
emplified in the numerous functional relationships 
between organs. This altruistic function is of ex- 
treme importance, for the cell itself may seem to 
all intents and purposes quite healthy and yet still 
gravely fail in its altruistic functioning — a failure 
which, small though it be, may suffice to disorgan- 
ize the delicate hormonic balance. Granting, then, 
that chronic disturbances are associated with gen- 
eral cellular inactivity and that in certain condi- 
tions this deprives the body of essential stimuli, 
it must be obvious that the effective treatment of 
such conditions must include a consideration of the 
ductless glands and of means capable of re-estab- 



168 THE INTERNAL SECRETIONS 

lishing the normal production of their hormones. 

One of the most common disorders in which so- 
called "pluriglandular insufficiency" is evident is 
neurasthenia, in which there may be no positive 
evidence of defective action of a gland or series of 
glands. It is obvious that in the majority of such 
cases there must be a disturbed endocrinism, for it 
is hardly reasonable to suppose that in an individ- 
ual with prominent manifestations of half-speed 
function, such as constant fatigue on slight exer- 
tion, defective oxidation as evidenced by low urin- 
ary solids, nerves that are easily set ''on edge," cir- 
culation that is poor, with cold, clammy extremi- 
ties, and not infrequently reduced tension, ambi- 
tion and mental powers much below par, and the 
like, the production of the essential chemical mes- 
sengers is not reduced just as are all the body activ- 
ities. This being the case, pluriglandular therapy 
not only serves to replace, in however slight de- 
gree, the missing secretions, but favors an in- 
creased production of them by the homostimulant 
action already referred to. 

Theoretically this sounds very plausible and 
practically it has been found to work very nicely. 
Pluriglandular therapy is undoubtedly empirical, 
for in the class of cases under discussion at least, 
there is no definite proof as to which of the ductless 
glands is deficient and to what extent. For this 
reason it has been ridiculed by some who forget 
that nine-tenths of our present therapeutics was at 



IN PRACTICAL MEDICINE 169 

one time purely empirical, while a good share of 
it still has no positive scientific basis. A procedure 
that has secured results before may do so again, 
hence it is worth trying. This is the present posi- 
tion of pluriglandular therapy, and it is believed 
that the successes already obtained are an earnest 
of what is in prospect. 

Another important series of chronic conditions 
which must at least be mentioned in passing are 
the functional neuroses and psychoses, many of 
which are now earmarked as resulting from or be- 
ing intimately associated with disordered secre- 
tory action of certain of the ductless glands. In a 
recent paper in the American Journal of Insanity, 
Murray Auer concludes that the glands of internal 
secretion mutally influence functional activity and 
the occurrence of insanity at puberty and adoles- 
cence, after severe physical and mental strain, and 
at the time of the menopause (all periods when the 
metabolic changes of the body are intense), and 
the occurrence of syndromes unquestionably the 
result of disease of the endocrine organs, insan- 
ity, idiocy, debility, mania and dementia, suggest 
strongly that the true etiology of the affective psy- 
choses lies in functional disturbances of the glands 
of internal secretion. 

Many of the problems of the medical gynecolo- 
gist have an altogether endocrine origin, and the 
metabolic disturbances of women constitute a large 
class of chronic diseases in which organtherapy is 



170 THE INTERNAL SECRETIONS 

an extremely useful measure. Substitutive organo- 
therapy is an every-day measure of the most pro- 
gressive gynecologists and the subject is far too 
large to discuss here. The value of the extracts of 
the corpus luteum in ovarian hypofunction, as well 
as the homostimulant action of the same substance 
in less serious conditions, is becoming increasingly 
apparent. Pituitary extract is nov^ used in a great 
many cases of this class, not merely for its obstet- 
rical virtues but as a means of re-establishing a 
disturbed balance in cases like amenorrhea and cer- 
tain forms of dysmenorrhea. 

One of the most neglected organotherapeutic 
remedies in gynecological practice is the extract of 
the mamma, about v^hich I cannot refrain from say- 
ing a few words. Briefly, the mamma is also an 
internal secretory organ and is the direct antag- 
onist of the ovaries, hence extracts thereof may be 
of value in the control of conditions due to super- 
activity of the ovaries. The principal among these 
are menorrhagia, metrorrhagia, and uterine 
fibroids. I know the surgeons will disagree, but 
the fact remains that functional uterine hemor- 
rhage (not due to foreign bodies or organic condi- 
tions) is frequently controlled better by a course 
of mammary extract than by any other means and 
there is a rational physiological reason for this 
benefit. A number of Russian investigators have 
shown that the use of mammary substance is of 
extreme value in many cases of fibroids and those 



IN PRACTICAL MEDICINE 171 

who may be especially interested in this subject 
might with an advantage read a paper which I 
have prepared for a Special Internal Secretion Is- 
sue of the Woman's Medical Journal for March, 
1915.* Suffice it to say that enough evidence is 
gathered together there to warrant the use of 
mammary extract for a period before operative pro- 
cedures are taken and the aggregate results are 
sufficiently good eventually to bring this method 
of treatment into much higher esteem and fre- 
quent usage. 

[Within the past year (1917) I have had 
occasion indirectly to note the clinical value of this 
phase of treatment in a case of well-advanced can- 
cer. A colleague, interested in organotherapy, 
was recommended to try mammary substance in 
a case of uterine carcinoma in an old woman. There 
was much hemorrhagic oozing, as well as very bad 
odor. Twenty grains of mammary substance were 
administered each day for a week and the dose then 
increased to 30 grains. The treatment was sug- 
gested by me in the hope that the oozing which 
had persisted for months despite various internal 
and local treatments, might be staunched. I was 
particular to emphasize the slimness of the pros- 
pects and that the method was really offered as n 
last resort. 

Not only was the hemorrhage stopped but the 
odor was considerably diminished and the patient 

*See Chapter XVI. 



172 THE INTERNAL SECRETIONS 

even began to assure her family that she was going 
to get well, since her strength really did improve 
quite considerably. The doctor, however, took 
pains to inform them that the treatment was 
merely having an effect upon the blood supply of 
the affected organ and not upon the disease itself, 
and even so this seemed to all concerned to be a 
very distinct vindication of the anti-hemorrhagic 
effect upon the uterus of mammary substance.] 

You will note that I have said nothing about the 
use of thyroid extract in the chronic and well- 
known conditions associated with thyroid defi- 
ciency, nor can I take time to outline the advan- 
tages of pituitary extract in those equally chronic 
conditions of hypopituitarism. In fact, organo- 
therapy is principally useful in chronic disease, 
anyway, and to consider the matter as thoroughly 
as the subject deserves would keep us too long. 

We now come to the second and perhaps the 
more important part of this paper — the relation of 
the glands of internal secretion to cancer and the 
possibilities of organotherapy in this condition. 
This is neither the place nor the time to discuss 
the physiological basis of cancer or to speculate 
upon the how or why of this disease. We may, 
however, enumerate several promising and quite 
thoroughly substantiated theories: (1) Cancer is 
a chronic intoxication; (2) its incidence evidences 
the lack of an element in the blood which permits 
cell proliferation at a point of particularly lowered 



J 



IN PR.\CTICAL MEDICINE 173 

resistance; (3) it is essentially a disease of senes- 
cence or, as Hastings Gilford has termed it, ''cell 
senilism.'' 

Seven or eight years ago many hopes were raised 
following the publication of the results of work 
done by Dr. John Beard of Edinburgh, and quite 
an impetus was given to the study of organother- 
apy in cancer because of the fact that trypsin w^as 
then brought forward in medical and, unfortu- 
nately, lay magazines as ''worthy of immediate 
trial in the behalf of the many persons to w^hom it 
offers a possible chance of escape from an other- 
wise inexorable fate." Seemingly the attention ot 
the public was drawn prematurely, for there has 
been no remarkable reduction in the mortality sta- 
tistics nor do any of us here consider that pancre- 
atic ferments are more than an incidental measure 
of relief in cancer. 

It must be admitted, however, that Beard's work 
virtually inaugurated a more enthusiastic and 
searching consideration of organotherapy in can- 
cer and while we have advanced many steps since 
1906 we must not be satisfied yet. In the words of 
a recent writer: "We have survived too many hy- 
potheses in regard to this elusive disease to accept 
further generalizations however plausible they 
may be at first inspection of the evidence; yet we 
are always glad to recognize every scintilla of a 
new suggestion which may furnish a welcome 
guide to progress." 



174 THE INTERNAL SECRETIONS 

With the foregoing in mind it may be well to col- 
late a number of ideas which indicate a relation- 
ship between the incidence of cancer and ductless 
gland disorder, so that we may use them as a foun- 
dation for possible lines of treatment in this direc- 
tion. They may also serve as a basis for explain- 
ing the not infrequent reports of the good results 
from organotherapy in cancer which are to be 
found in the literature. 

We know that cellular activity is influenced by 
the hormones, or chemical messengers, that nutri- 
tion responds in a greater or lesser degree to their 
influence, and that it is possible to favor the reac- 
tion of the body against disease by the ingestion of 
ceritain organic extracts. The first question which 
naturally suggests itself is: Is not cancer more 
than a chronic disease such as the more benign 
metabolic disturbances previously referred to? Is 
it possible to influence by means of organotherapy 
an unquestionably organic condition when the ac- 
tion of the endocrine principles is supposed to 
be upon function rather than upon structure? Un- 
doubtedly no form of internal medication at pres- 
ent known will destroy or remove the fundamental 
organic conditions pathognomonic of cancer, but 
it is entirely possible that the resistance of the suf- 
ferer from cancer may be increased to such a de- 
gree that other measures in common use may be 
backed up by an increase in the responsiveness of 
the cells and a general enhancement of nutrition. 



IN PRACTICAL MEDICINE 175 

Some individuals, for reasons at present only 
premised, present a special receptivity to the im- 
plantation and growth of cancer cells. Why this 
should be so and just how the cells become im- 
planted is not for us to consider here, although it 
is a very fascinating subject and will, I believe, 
some day be thoroughly elucidated. I think it 
will be found to be much more intimately concerned 
with the internal secretions than is at present gen- 
erally believed. 

Clinically, the one essential symptom of cancer 
is waning cellular activity. Almost invariably nu- 
trition is poor and with few exceptions cancer is 
limited to individuals past the prime of life, a fact 
which indicates there may be a direct connection 
between the activity of those organs of internal se- 
cretion whose work ceases at this period and 
whose action is no longer needed. Experimentally 
it seems to be proved that there is a basis for the 
idea that the susceptibility to the implantation of 
the cancer cells is in some way related to the 
gonads and evidence of this is to be found in the 
investigations of Sweet, Corson-White, and Saxon 
of Philadelphia, who found that when tumors were 
transplanted into animals (mice) which had previ- 
ously been castrated the frequency of the estab- 
lishment of the cancerous implant, as well as the 
rapidity of its proliferation, was considerably more 
noticeable in the animals that were thus rendered 
more susceptible. 



176 THE INTERNAL SECRETIONS 

If we admit that an important factor in all can- 
cer cases is chronic cellular intoxication, then ob- 
viously a part of the treatment consists in favor- 
ing the activity of the known detoxicating organs 
as well as removing all nidi of further trouble, 
chiefly, of course, in the alimentary canal. The 
thyro-parathyroid apparatus is intimately con- 
cerned in the destruction of toxins and it is not re- 
markable to find a number of references in the lit- 
erature to the fact that in cancer subjects the thy- 
roid is usually found to be more or less atrophied. 
Parenthetically, it may be remarked that thyroid 
hypofunction is very much more common than 
until recently has been believed, and it is entirely 
possible for the thyroid cells to be seemingly nor- 
mal from a pathological standpoint and yet be 
failing very materially in the production of those 
substances which are responsible for the carrying 
out of the "altruistic work'' of this gland. Of course 
there has been considerable opposition to any the- 
ory which definitely connected the thyroid with 
this disease for thyroid therapy will be found to 
have practically no influence at all upon cancer. 

The association of intestinal fermentation, how- 
ever, has long been observed in cancerous indi- 
viduals and has even formed the basis of several 
theories as to its etiology. One of the well known 
manifestations of the cancerous cachexia is achlor- 
hydria and the resulting digestive disabilities. For 
this reason I recommend as a reasonable organo- 



IN PRACTICAL MEDICINE 177 

therapeutic procedure in all cases of cancer the at- 
tempt to re-establish the activties of the digestive 
glands by the administration of secretin. This ali- 
mentary hormone, secured from the duodenal 
walls, is a physiological means of stimulating the 
functionally inactive glands of the pancreas, liver, 
and intestines. Another sound reason for this par- 
ticular adjunct measure lies in the fact that the ab- 
sence of HCl from the stomach removes the normal 
stimulus to secretin production, since prosecretin 
is converted into secretin and released from the 
duodenal walls only by contact with the acid 
chyme, which is practically always absent in can- 
cer. Further, since the action of secretin is not 
limited to the digestive glands themselves, but also 
distinctly favors the production of secretin in the 
duodenum itself, its value should be doubly evi- 
dent, and the advantages accruing from the en- 
hanced digestion resulting from this procedure re- 
duce the toxemia normally present in cancer and 
at least must be considered one factor, even though 
a small one, in the treatment of this disease. 

The second of the postulates previously set forth 
suggests the absence from the body of a certain 
element, or series of elements. Just what is miss- 
ing from the blood of the cancerous is not yet well 
known, although the work of Abderhalden and 
those his research has stimulated indicates a defi- 
nite series of substances may be concerned in this 
matter. Weiss has gone so far as to show that 



178 THE INTERNAL SECRETIONS 

serodiagnostic tests demonstrate an opposite be- 
havior on the part of the serum from cancer pa- 
tients and normal serum, and that this definite lack 
permits cancer cells to proliferate, principally at 
parts exposed to mechanical stress or irritation. 
He even suggests it may be possible to isolate from 
normal serum the element in question, the lack of 
which permits malignant proliferation, and utilize 
this in the prophylaxis and treatment of cancer. 
However near this may be to the truth, it will ob- 
viously be an extremely difficult matter to make 
practical use of it, at least to any considerable ex- 
tent, and we must look still further for encourage- 
ment. This missing element, to my mind, will 
likely be found to be produced by the endocrine 
system, and, since the evidence already deduced 
indicates that his is not an unreasonable premise, 
the therapeutic possibilities are materially in- 
creased, for we now know with considerable cer- 
tainty that when there is a functional hypoendo- 
crinism or reduction in activity or service to the 
body of certain of the internal secretory organs, 
not only can the missing substances be replaced, 
but the semi-active organs may be stimulated by 
certain organic extracts in accordance with Hal- 
lion's law of homostimulation: "Extracts of an 
organ exert on the same organs an exciting influ- 
ence which lasts for a longer or shorter time. When 
the organ is insufficient it is conceivable that this 
influence augments its action and, when it is in- 



IN PRACTICAL MEDICINE 179 

jured, that it favors its restoration.'' Resulting 
from these and similar premises quite a number of 
attempts have been made to use organic extracts 
alone and in various combinations as a part of the 
treatment of cancer. While we have not yet found 
an ideal remedy, it seems certain that organic ex- 
tracts do produce beneficial results of varying de- 
gree. 

The spleen and thymus offer probably greater 
possibilities than many of the other glands, al- 
though I think that eventually the optimum prep- 
aration will be a pluriglandular extract containing 
these and other synergists. The therapeutic ad- 
ministration of spleen extract increases nutrition, 
of that I am quite convinced, and those who have 
followed the work of Bayle of Cannes in the use 
of spleen emulsions and extracts in the treatment 
of tuberculosis cannot but be convinced that there 
is good reason for his success. His report to the 
International Congress on Tuberculosis in Rome is 
extremely interesting. I have personally had a 
number of communications from this gentleman, 
as we have for some years been mutually interested 
in each other's work, and when the war started he 
was engaged in translating my book into French. 

Bayle's explanation of the sometimes remark- 
able influence of spleen extract is based upon what 
he calls its ''colloidogenic" action. His theory is 
this: The blood contains the mineral elements in 
two forms — (1) Those in a colloid state suitable 



180 THE INTERNAL SECRETIONS 

for cellular appropriation, and thus not suited for 
elimination by the kidneys, and (2) the mineral 
cellular wastes, which are dissolved in the plasma, 
and are destined to be eliminated. If the colloid 
elements lose their colloidal form they are 
promptly eliminated and a condition of demineral- 
ization obtains. The capacity to maintain the min- 
eral salts in a colloidal state is evidently of consid- 
erable importance, and, according to Bayle, seems 
to belong to the spleen. Bayle states that he has 
always found that splenic opotherapy quickly re- 
duces an excessive elimination of phosphates in 
the urine. All of this deserves to be tested experi- 
mentally and clinically. 

Now, there is undoubtedly a condition of min- 
eral starvation in all cachectic states, including 
that of cancer. This has been frequently mentioned 
in the literature, and is referred to in an editorial 
in the Journal of the American Medical Associa- 
tion in the following words: "This is, however, 
little less than the metabolic story of partial inani- 
tion which attends the cachectic states which ac- 
company so many chronic diseases. The demin- 
eralization, that is, the gradual and undue loss of 
all inorganic elements from the organism, is like- 
wise not to be regarded as characteristic of cancer 
alone." This is admitted, for one of the principal 
manifestations of tuberculosis is this very condi- 
tion, which explains Bayle's suggestions and his 
successful application of splenic-opotherapy in the 



IN PRACTICAL MEDICINE 181 

treatment of tuberculosis. There is no reason, 
however, why the same fundamentals should not 
be as applicable in the therapy of cancer as of tu- 
berculosis, and this may be an explanation of the 
good results occasionally reported from the use of 
spleen extract. 

Another gland frequently classed with the 
spleen, or at least with the lymphatic glands, is 
the thymus and more clinical work seems to have 
been done with thymus extract in cancer than with 
any other single extract. In 1907 Dwyer reported 
a number of cases that were benefited by this form 
of treatment and the more recent experimental re- 
searches of Rodenburg, Bullock, and Johnson, of 
this city, seem to prove that the products of the 
ductless glands are destined to play a certain role 
in our fight against cancer, and their recommenda- 
tions include the use of thyroid, thymus, and other 
extracts as part of the treatment. 

Some very interesting work in the study of can- 
cer has been done by Dr. Seelye W. Little of Roch- 
ester, N. Y., and as a result of this he outlines cer- 
tain facts which he has inferred from quite a num- 
ber of clinical experiences. In the main his con- 
tention is that the reproduction of the reverted cell 
types in cancer is caused by the relative hypofunc- 
tion of certain of the ductless glands and that to 
produce a cancerous growth such hypofunction 
must be primarily in an internal secretory organ 
derived from the same blastodermic layer as are 



182 THE INTERNAL SECRETIONS 

the cells from which the cancer originates. As a 
result of this he suggests that mammary carcinoma 
implies hypofunction of some endocrine organ de- 
rived from the ectoderm, since the breast is ecto- 
dermic in origin. He has also shown that the met- 
abolism of sugar and calcium are intimately con- 
nected with the disordered nutrition of cancer and 
connects this in a very convincing manner with 
those glands which exert a vital relation to the 
metabolism of sugar or calcium or both. 

Little's experiences are fascinatingly outlined in 
his papers published in the Boston Medical and 
Surgical Journal last year, to which the careful 
attention of every student of this subject should be 
drawn. His clinical findings warrant the use of 
several organic extracts, principally from the pitu- 
itary, parathyroid, adrenal cortex and the islands 
of Langerhans. In his most recent paper, in addi- 
tion to emphasizing the value of sugar feeding in 
many cases of cancer, he has settled down to three 
ductless gland extracts as essential, one each for 
ectodermic, mesodermic, and endodermic cancer. 
For the first he uses total pituitary extract; for the 
second an extract of the adrenal cortex; and for 
the third an extract of the pancreas rich in the 
islands of Langerhans. All through his communi- 
cations there is an underlying element of judicial 
research. He is not ultra enthusiastic and does not 
claim to have discovered a panacea for cancer. One 
cannot but believe from the clinical results of his 



IN PRACTICAL MEDICINE 183 

work that he is on the right track and that the con- 
clusions which may be drawn from some of the 
facts gathered together here this evening warrant 
the continued investigation by a much larger num- 
ber of students of the subject, not only of the rela- 
tions of the ductless glands to the incidence of can- 
cer, but the prophylactic and direct treatment 
thereof by organotherapy. 

The third essential concerns the relation of the 
incidence of cancer to senility. We cannot deny 
that senility is the result of changes in certain of 
the internal secretory organs and that by far the 
greatest cancer incidence will be found in individu- 
als well past the apex of vital activities. Just as 
fungus growths are usually found on decaying 
trees, so the similar cancerous manifestations are 
evidences of senile decay. Dr. Hastings Gilford of 
Reading, England, writes occasionally on the vari- 
ous subjects connected with senility and the duct- 
less glands, and while at times he delves deeper 
than I am able to fathom, he is undoubtely cor- 
rect in his theories regarding cancer, that it is 
essentially a form of cell senility. He says that 
"certain somatic cells become dead while the tissue 
around them is still in a state of comparative youth. 
They express their senility by returning to a more 
embryonic form and as they do so they increase in 
number, the faculty of proliferation being one of 
the manifestations of regression." These senile 
changes may be presumed to be connected with 



184 THE INTERNAL SECRETIONS 

disturbances in the hormone balance. 

This brings us to the consideration of another 
important phase of this subject — whether it is pos- 
sible to use these organic extracts as prophylactic 
agents. I think it may be, but it is very difficult to 
know how and when to begin, for usually patients 
suffering with cancer do not give us the oppor- 
tunity of investigating their trouble until the dis- 
ease is well established. 

Dr. Robert Bell of London has written telli^ig 
''How to Destroy the Cancer Scourge," and aims 
to do this by restoring the vital energies of the 
whole cellular structure by what he considers to be 
a suitable diet. Unfortunately, however, recourse 
to this diet does not seem to have become the 
fashion yet, and the scourge is not being destroyed. 
The cancerous individuals are always run down; 
they are in a state of receptivity to disease and are 
obviously sufferers from pluriglandular insuffi- 
ciency. If this subject is more carefully studied — 
it is remarkable how extended are its ramifications 
and how practical are the resulting clinical deduc- 
tions — the reasonableness of this position may be 
clear to you. In other words, suitable combinations 
of glandular substances may be given empirically 
where a more or less obvious deficiency is pre- 
sumed. 



( 



XV 

SOME REMARKS ON THE TREATMENT OF 
HYPERTHYROIDISM 

THE editorial invitation extended in a recent is- 
sue of Clinical Medicine, to ''throw more light on 
this subject" of hyperthyroidism, prompts the fol- 
lowing remarks, which, it is hoped, may be of inter- 
est because of the numerous and widely differing 
measures suggested in current medical literature 
for the treatment of thyrotoxicosis, or hyperthy- 
roidism. 

To my mind, there are three important things to 
accomplish or to attempt to accomplish in the treat- 
ment of this troublesome condition; namely: 

First, the control of the toxemia, and especially 
of its serious cardiac manifestations; 

Second, the removal of the sundry and widely 
differing causes of the thyroid irritability; and 

Lastly, the re-establishment of the deranged 
metabolism and the ''building up" of the badly dis- 
organized cell nutrition. 

The immediate treatment of cases of hyperthy- 
roidism, in my estimation, centers on the control of 
the heart's action; and this is accomplished most 
satisfactorily by placing the patient at absolute rest 
in bed, in a quiet room away from the numerous 



Reprinted from The American Journal of Clinical Medicine 
(Chicago), April, 1917. 

(185) 



186 THE INTERNAL SECRETIONS 

worries and noises of the home. Cold applications 
over the region of the heart and of the thyroid 
gland exert some beneficial effect. 

By far the most important remedy, in my expe- 
rience, is the extract of the posterior lobe of the 
pituitary, which may be given, by intramuscular 
injection, daily in doses of a 1-2 to 1 mil (Cc.) of 
the usual standard solution. I have had occasion 
to use numerous sedative remedies, and none 
seemed to exert so particularly beneficial an effect 
as this organotherapeutic wonderworker. 

The usual effect of these injections is, the reduc- 
tion of the pulse rate by from 30 to 70 beats a min- 
ute, while, by its remarkable influence upon so 
many functions, it also favors the intestinal activi- 
ties as well as increasing diuresis. According to 
Pal, the principle of the posterior pituitary lobe ap- 
pears actually to exert a well-defined antagonistic 
action upon the unruly thyroid gland. Whether 
the pituitary gland contains a principle that exerts 
an effect opposite to that of the thyroid gland (an 
antihormone), has not been established; still, I am 
convinced that, clinically at least, pituitary therapy 
is as profitable an advance in the treatment of hy- 
perthyroidism as is any measure suggested in the 
past and deserves much wider application and 
study in practice. This matter will be referred to 
again shortly. 

Since it is imperative to accomplish some imme- 
diate and tangible results by the symptomatic 



IN PRACTICAL MEDICINE 187 

treatment of the patient and particularly the heart's 
action, it is in order carefully to investigate every 
possible source of toxemia and to antagonize it to 
the best of our ability. Undoubtedly the most fer- 
tile field for toxemia is the intestinal canal, and my 
routine treatment in such cases, instead of resort- 
ing to purging-treatment by mouth (toxins re- 
leased by vigorous purging exert a very unfortu- 
nate eitect upon the symptoms and have, indeed, 
led to the dismissal of the physician because of the 
severe reaction following the well-meant and none 
the less much-needed treatment), is to prescribe 
a series of oil enemata administered on three suc- 
cessive evenings. These enemata should consist of 
5 or 6 ounces of any convenient oil (cotton-seed, 
olive, almond), warmed to the body-temperature 
and injected with an ordinary bulb-syringe, being 
made, by position and gravity, to reach the farthest 
end of the large intestine. This injection is to be 
retained all night. It has been found that its repe- 
tition on the second and third nights may bring 
away still more impacted material that was not 
loosened by the first one. 

Parenthetically I will mention that many sub- 
jects of hyperthyroidism have an associated condi- 
tion that might properly be called mild mucous 
colitis, and I am beginning to believe that there 
subsists a distinct relation between this disease and 
serious endocrine disturbances. At all events, where 
intestinal irritability is discovered and the patient 



188 THE INTERNAL SECRETIONS 

has been passing more or less mucus, 1 ounce of 
the pint of oil may be replaced by 1 ounce of ich- 
thyol (or, as I have been using more recently, 
ichthyonat), which suffices to soothe the intestinal 
wall while it also exerts a certain degree of anti- 
septic action. 

If laxatives are prescribed, they must be of the 
gentlest-acting nature. Cathartic pills, pills of aloin, 
belladonna and strychnine, and active alkaloid- 
containing stimulants are not advisable, because of 
their vigorous action and also because of a fre- 
quently undesirable simultaneous effect upon the 
heart. 

The next procedure consists in neutralizing the 
alimentary toxemia as far as possible and, at the 
same time, since it has been demonstrated beyond 
question that the majority of the alimentary wastes 
are acid in reaction, alkaline treatment is in order. 
It is my custom to direct the patient to drink dur- 
ing the twenty-four hours at least 3 pints of water 
in which from 60 to 100 grains of sodium bicarbo- 
nate is dissolved, but laying strong emphasis on 
the necessity for not taking any of the alkaline 
water within one hour before or three hours after 
meals. If a 2-quart Mason jar is filled three-fourths 
full with water and the soda is dissolved in it, not 
only does it facilitate the measurement, but the 
sight of it, in a conspicuous place, serves as a re- 
minder, toward the close of the day, whenever the 
patient has not been drinking the amount ordered. 



IN PRACTICAL MEDICINE 189 

Furthermore, the fact that the water contains a 
prescribed remedy and the reason for its adminis- 
tration has been made clear, prompts the patient to 
overcome any difficulty he may experience in dis- 
posing of this quantity (unfortunately, it is not the 
rule, in these cases at least, to drink sufficient 
water), for he realizes that it is not merely the 
drinking of water but the following out of a part 
of the doctor's course of treatment. In addition to 
the foregoing, I frequently have prescribed the 
combined sulphocarbolates as a means of keeping 
the intestine as nearly aseptic as possible. The dose' 
should be at least 30 grains a day; however, it 
seems poor policy to waste good medicine of this 
character by not first giving the intestine a thor- 
ough cleaning out. In other words, the sulpho- 
carbolate tablets must not be prescribed until the 
fourth day of treatment. 

Occasionally in severe cases there is a more or 
less intractable diarrhea, and for the control of this 
feature I have been using protan with success. 

The intestine by no means is the only source of 
toxic substances that irritate the thyroid gland. 
Thus, it has been found quite frequently that pyor- 
rhea is an accompanying disturbance in these cases, 
so that this condition must be treated locally, and 
thoroughly. The use of iodoglycerol as a local anti- 
septic and as an indicator of ''dirt" on the teeth 
(which latter must be removed mechanically) is 
of great advantage. Various antiseptic dentifrices 



190 THE INTERNAL SECRETIONS 

and mouth-washes profitably may be recommended, 
while I have seen injections of emetine bring about 
very favorable effects, not merely upon the amebi- 
asis, but also upon the thryoid gland and its func- 
tioning. 

Other common sources of irritation of the thy- 
roid gland are: diseased tonsils and infected nasal 
sinuses (frontal, ethmoid or sphenoid), pelvic in- 
fections, and, incidentally, local trouble in the 
angles of the intestine, the gall-bladder, and else- 
where. 

The doctrine of focal infection was never more 
applicable and practically useful than in the "diag- 
nostic treatment" of thyroid disorders, and many a 
failure satisfactorily to control dysthyroidism has 
been owing, not so much to inappropriate treat- 
ment, as to the fact that some hidden source of 
toxemia was overlooked. 

Before leaving the sources of thyroid irritation, 
emphasis must be laid 'on still one other very im- 
portant cause of functional thyroid troubles. We 
are now convinced, by the writings of Elliott (Lon- 
don), Sergent (Paris), and Cannon (Boston), that 
the emotions exert a specific effect upon the chem- 
istry of the body, through the faculty of the adrenal 
glands to respond to emotional stimuli. Fear, rage, 
pain, and even worry, all excite the chromaffin sys- 
tem and through this effect cause sensitization or 
irritation of the entire sympathetic mechanism. 

A case of exophthalmic goiter is on record which 



IN PRACTICAL MEDICINE 191 

developed suddenly, as from a clear sky, immedi- 
ately following the mental strain imposed by the 
San Francisco earthquake. I have seen a number 
of cases recently in which the emotional element 
was unfortunately prominent. One case in par- 
ticular originated from the shock of an insignificant 
fall of a foot or two. Another was aggravated by 
family troubles, while a third one, progressing 
nicely under my routine treatment, was set back 
abruptly and the pulse bounded up 40 beats a min- 
ute because of the excitement accompanying a sud- 
den sickness of another member of the family. 

Unfortunately, the control of the mental and 
psychic influences is most difficult; nevertheless, it 
IS of highest importance to attempt as best one may 
the removal of the sources of psychic irritation — 
fear and worry, and, be it remarked, much "com- 
pany" and exciting reading. 

Practically all subjects of hyperthyroidism are 
poorly nourished, despite the fact that they may be 
hearty eaters and their digestion may seem to be 
perfectly normal. The reason for this is, of course, 
that the thyroid gland controls cell nutrition and 
the excessive stimuli coming from this gland, as 
the result of its disordered function, cause the foods 
to be burnt up too rapidly; malnutrition and even 
emaciation, hence, being the rule. 

For this reason, the dietary must be generous 
and fattening. In addition to three liberal meals 
containing as few purin-bearing articles as possible, 



192 THE INTERNAL SECRETIONS 

I am in the habit of prescribing buttermilk pre- 
pared with a reHable culture of the bulgaric bacillus 
and to be drank at least twice a day, conveniently 
fitted in between the meals; and crackers with the 
buttermilk, if the patient cares for them. I am also 
partial to ice-cream as a daily adjuvant to the diet- 
ary, not merely because of the gustatory pleasure 
it affords, but because of its high caloric value. 

Another article of the diet suggested — one pos- 
sibly not possessed of any well-defined nourishing 
value, but which is of undoubted service, not alone 
in this disease, but in many nutritional disorders, 
is a rich vegetable consomme prepared by cooking 
together various and differing combinations of veg- 
etables, especially the green stuffs. In these, I in- 
clude: spinach, beet tops, turnip tops, celery (in- 
cluding the leaves), celeriac, asparagus (not in ev- 
ery case, because of the renal stimulant present), 
tomatoes, fresh young peas (with pods included), 
stringbeans, turnips, potatoes, in fact, almost any 
vegetable, boiling them in sufficient water for a 
long enough time completely to extract the saline 
elements, so that they may serve as an efficient 
nutrient instead of being thrown away, as is the 
rule in our present wretched cookery. Needless to 
repeat here that these vegetable salts are of real 
value in many disorders of metabolism, and, surely, 
it is correct to put hyperthyroidism in this cate- 
gory. Incidentally, the cook can modify the flavor 
and color of the consomme and change its concen- 



IN PRACTICAL MEDICINE 193 

tration at will; the form of serving may vary from 
a hot cup to jelly (made v^ith pure gelatin) ; it may 
be given iced or frozen; also, it makes a very pal- 
atable dietetic adjuvant in many conditions. 

Not infrequently the oral administration of pan- 
creatin may prove of distinct advantage, and I 
sometimes think that it has a dual action, in not 
merely increasing the digestion and, hence, favor- 
ing the assimilation of more much-needed food, but 
also acting upon the sympatheticotonic condition 
characteristic of this malady. 

A w^ord of explanation may here be in order. 
Toxemia having its origin in the thyroid gland or 
from any other cause, including the emotional stim- 
uli referred to, gives rise to hyperadrenia; in fact, 
hyperthyroidism nearly alv^ays is accompanied by 
hyperadrenia, as may be quickly demonstrated by 
the application of Loew^i's instillation test (put- 
ting one drop of adrenalin solution into the con- 
junctival sac and observing its influence upon pupil- 
lary action).* The dry mouth, the tremor, and some 



* Quoting from W. M. Barton's excellent little "Manual of 
Vital Function Testing Methods and their Interpretation" (Bos- 
ton, Richard G. Badger): "In 1908 Loewi made the observa- 
tion that after removal of the pancreas in certain animals, the 
installation of adrenalin into the eye will cause dilatation of the 
pupil. Loewi attributed the mydriasis to increased excitability 
of the sympathetic system brought about by the removal of the 
inhibitory effect of the pancreatic internal secretion." 

This has been used successfully in diabetes mellitus, but it 
will also be positive in Graves' disease due to the increased 
sympatheticotonus. Hence it is valuable in both these condi- 
tions, the reaction in the former being due to a deficiency 
brought about by the lack of the pancreatic hormone and in the 
latter to an excess of the chromaffin hormone (the mutual an- 
tagonist to the pancreatic hormone). 



194 THE INTERNAL SECRETIONS 

of the other nervous manifestations seem to me to 
be as much of adrenal as of thyroid origin. Now, it 
happens that the internal secretion of the pancreas 
exerts a decided antagonistic action upon that of 
chromaffin cells, and, in fact, it has by some been 
called the "pancreatic anti-hormone"; henoe, any 
means of facilitating this function of the pancreas 
(in addition to its external secretory powers) is 
distinctly in order. 

The administration of pancreatin not merely as- 
sists in digesting certain foodstuffs in the bowels, 
but, like all organotherapeutic measures, brings 
about a homostimulant action or, in other words, 
it favors the work of the pancreas, increasing the 
output of its chemical substances. Within the past 
year, several communications regarding the use of 
pancreatin in hyperthyroidism have appeared in 
print, and, as for myself, while I do not think of 
making it the main treatment, I consider that 15 
to 30 grains or more per day, given after meals, 
certainly makes a useful adjuvant. 

All the above seems to be of practical value, while 
I have purposely refrained from commenting upon 
the fairly well-known drug-treatment and the con- 
sideration of the need for surgery and Watson's 
excellent quinine-urea injection-method, all of 
which are the subjects of recent communications. 

I cannot refrain, however, from recommending 
the method of treatment suggested last year by Dr. 
George Richter, of St. Louis, which consists in the 



IN PRACTICAL MEDICINE 195 

daily administering from 15 to 30 grains of the 
desiccated anterior lobe of the pituitary body. I 
have adopted this treatment in the case of 11 pa- 
tients, some of them ambulatory and others rest- 
ing in bed, and am convinced that there is brought 
about a valuable sedative action that is of distinct 
advantage, and I am hoping to be able some day to 
say definitely that this endocrine organ is the rem- 
edy for hyperthyroidism. At present, I can recom- 
mend it as a very useful adjunct to the other treat- 
ment above outlined, v^hich has become a routine 
in my hands because of its effectiveness and rea- 
sonableness. 



XVI 

THE MAMMA AS AN INTERNAL SECRE- 
TORY ORGAN: MAMMARY 
THERAPEUTICS 

IT is surprising how many of the glandular 
structures of the body whose secretory activities 
are so well known are beginning to be classed as 
having an additional and equally important func- 
tion, i. e., that of internal secretion. It now seems 
beyond question that in addition to the pancreas, 
liver and gonads, the mammary glands also must 
be classed among the organs with a dual function, 
that of the production of both internal and external 
secretions. Incidentally, there seems to be some 
basis for the belief that the parotid is another of 
the glands with ducts which must be considered as 
having an internal secretion as well as an external 
secretion. 

The fundamentals which serve as the basis of 
this paper may be summarized in the following 
postulates: (1) The mammae, in addition to their 
galactogenic function, produce an internal secre- 
tion, are themselves subject to hormone influences, 
and hence must be considered as part of the en- 
docrine system. (2) Suitably prepared extracts of 
the mammary parenchyma contain a principle (pre- 
sumably a hormone) which exerts a definite physi- 



Reprinted from The Woman's Medical Journal (Cincinnati), 
March, 1915 

(196) 



IN PRACTICAL MEDICINE 197 

ologic action, and hence have inherent possibilities 
of therapeutic utility. 

There are quite a number of reports of experi- 
ments made in different parts of the world which 
give abundant evidence of the truth of the first pos- 
tulate, a limited number of which will be referred 
to briefly here. It is convenient first to consider 
the hormone control of the mamma and later to 
mention its hormone influence upon other organs 
and functions. 

In 1906, in the Institute of Physiology, Uni- 
versity College, London, Starling"^ and his associ- 
ate, Miss Lane-Claypon, demonstrated that the 
fetus is the seat of the production of a hormone 
which, passing through the placental circulation to 
the mother, brings about a specific stimulation of 
the mammary glands, first to enlarge and later to 
perform their milk-producing function. This sub 
stance seems to be of a definite chemical nature, 
and may even be obtained from dried embryo sub- 
stance, from which it is extracted in a manner 
somewhat similar to the production of secretin from 
the mucosa of the duodenal walls. 

One of the most remarkable of all their experi- 
ments was the establishment of lactation in virgin 



*A pioneer in the study of the hormones, the discoverer of 
the "original hormone" secretin, and the originator of the term 
"hormone" (Gr., I arouse, excite or set in motion). Quite a 
full consideration of the history and importance of Starling's 
work with secretin, as well as of the importance of the discovery, 
production and action of hormones and the fundamental prin- 
ciples of hormone therapy will be found in my recent work, 
"Practical Hormone Therapy." 



198 THE INTERNAL SECRETIONS 

rabbits by the injection of these extracts. Several 
other investigators since have confirmed this work, 
and, in addition, have shown that fetal extracts 
from one animal will be active in bringing about 
this definite physiologic action in animals of a dif- 
ferent species. So far as I am aware, no use has 
been made of this in medicine, for obvious reasons. 
Be that as it may, this was an important revelation, 
although it was by no means the original work 
which showed that the mammary gland was influ- 
enced by the chemical messengers. The experi- 
ments of Ribbert, made in the late nineties, seem to 
be the first in this line, and while they did not quite 
reveal the character of the stimuli, they undoubt- 
edly proved that the development of the mammary 
gland was not solely under the nervous control. 
Ribbert and his associates transplanted a portion 
of the mamma from a virgin rabbit into a pregnant 
animal, and in due time the graft developed and 
actually secreted milk. 

The fetal hormone or, as it was originally termed, 
the "mamma hormone,"* is not the only chemical 



*The term "mamma hormone" is fortunately becoming rare, 
since, as will be seen later, this term properly designates the 
hormone produced in the mammae — not the hormone which 
activates them. Incidentally, it will be remembered by those 
acquainted with the remarkable results of the work done with 
secretin, that it was originally called "pancreatic secretin," not 
because it is produced by the pancreas, but because it activates 
it. It is now called "duodenal secretin," because it is produced 
in the duodenal walls, though, of course, it still remains the 
principal activator of the pancreatic glands. The later nomen- 
clature makes it possible to differentiate between secretins from 
varying sources, as, for instance, the gastric or pyloric mucosa. 



IN PRACTICAL MEDICINE 199 

messenger concerned in the control of the mam- 
mae, for it is evident that other hormone factors 
are concerned in the development and establish- 
ment of mammary activity. There is a very inti- 
mate relationship between the ovaries and the 
mammae, which has been demonstrated by Bouin 
and Ancel. These investigators found that by arti- 
ficially rupturing the luteal follicles of the ovaries 
of rabbits, in addition to causing the discharge of 
the ovum there was produced a chemical substance 
— a hormone — which causes a marked histological 
change in the mammary gland, quite apart from 
the presence of the products of conception in the 
uterus (for the rabbit was not pregnant). In con- 
sidering the reports of these remarkable experi- 
ments, an editorial writer in the Journal of the 
American Medical Association states that "these 
facts serve to lend new emphasis to the dependence 
of such physiologic response as mammary develop- 
ment on other than purely nervous relations. Thev 
add to the coming significance of hormone activi- 
ties in the interdependence of various parts of the 
organism." 

It is a well-known fact that experimental, as well 
as clinical, ovariotomy frequently is followed by 
retrogressive changes in the breasts and even by 
their disappearance, while experiments on animals 
have shown that under such circumstances an 
ovarian graft will bring about a re-establishment of 
the growth and activity of these organs. There 



200 THE INTERNAL SECRETIONS 

seems to be conclusive proof that the internal se- 
cretion of the ovary is a factor which controls or at 
least influences mammary activity. 

The study of mammary development may be 
quickly broadened into a study of the hormone in- 
fluences v^hich control these organs, and a very 
complete consideration of this subject forms the 
These de Doctorate of Schil (1912). A resume of 
Schil's v^ork v^ill be found in my book, "Practical 
Hormone Therapy," and I can do no better than to 
include a part of it here: 

Schil recognizes six stages in the evolution of 
the mammae: (1) The stage of development, di- 
vided into an organogenetic phase and a phase in 
v^hich there is secretory activity (the lactation of 
the new-born). This secretory phase is dependent 
upon a hormone passing from mother to fetus 
through the placenta. This same hormone activates 
mammary secretion in the mother. (2) The pre- 
pubertal stage, which lasts until puberty (or the 
first rut in animals), during which the glands are 
functionally inactive. (3) The stage of puberty, 
characterized by a considerable increase in the 
glandular parenchyma. This growth is dependent 
upon the exciting influence (by means of a hor- 
mone) of the mature Graafian follicles in animals, 
in which non-spontaneous ovulation is produced 
artificially, and in the case of spontaneous ovula- 
tion, to the follicles and corpora lutea, which de- 
velop from these follicles after dehiscence. (4) The 



IN PRACTICAL MEDICINE 201 

gravid stage, which is divided into two phases: a, 
Growth, especially evident during the early part 
of gestation, as a result of which the glands attain 
their complete development; and, b, a so-called 
"phase glandulaire gravidique," which follows the 
completion of growth and is characterized by se- 
cretory activity, the product of which is known as 
the "colostrum." Each of these two phases is the 
result of hormone action, the first due to a kineto- 
genic hormone from the corpus luteum of preg- 
nancy, and the second to a criticogenic hormone, 
which seems to come from a secretory portion of 
the placenta during the second part of gestation, 
or from a myometrial gland. (5) A post-partum 
stage, continuing during lactation until the glands 
are again in repose, and divided into two phases: 
a, Post-partum glandular activity, in which the 
milk is produced; and b, the phase of post-partum 
retrogression, in which galactogenesia ceases, and 
the parenchyma is slightly diminished. Of these 
two phases only the first is of interest, since the 
second is caused by the absence of stimuli. The 
milk, released during pregnancy by an endogenous 
stimulus, is maintained by an exogenous stimulus, 
the act of suction. (6) A senile stage, associated 
with involution, and corresponding to the period of 
cessation of genital activity. 

There is, of course, further proof of the intimate 
relationship between the mammae and ovaries, as 
for example, the well established fact that the oper- 



202 THE INTERNAL SECRETIONS 

ation of spaying dairy cows at the time of giving 
their greatest flow of milk has an influence upon 
the lacteal period. In a personal communication 
from the Bureau of Animal Industry the following 
appears: ''It is a well established fact that in 
spayed dairy cows the period of lactation is pro- 
longed." 

Additional emphasis is lent by the fact that the 
function of ovulation is retarded and sometimes 
entirely stopped during prolonged lactation, pre- 
sumably because in the stage of mammary activity 
the increased elaboration of the internal secretion 
antagonizes ovarian activity in a greater or less de- 
gree. It is well known that pregnant cows as a 
rule show a tendency to lessen the supply of their 
milk after conception takes place. 

In a conversation on this subject the other day, 
it was stated that quite frequently women with 
large mammary development menstruate scantily, 
while those with small breasts not infrequently are 
subject to menorrhagia. This is by no means al- 
ways the case, but it points at least to an antago- 
nism between the mammae and the ovaries. 

As still further incontrovertible evidence of the 
hormone control of galactogenesia I will cite the 
remarkable experience of the famous Blazek twins. 
It may be remembered that this pair of pyopagous 
female twins matured and one of them married. In 
due time she became pregnant and was success- 
fully confined and after delivery the secretion of 



IN PRACTICAL MEDICINE 203 

milk also took place in the non-puerperal sister. In 
other words, both were able to nurse the infant, 
and obviously the influences which stimulated 
mammary activity in the unmarried sister were of 
a hormone nature. 

Most of these facts, it is true, indicate that the 
mammae are subject to hormone influences — i. e., 
are controlled in part by an internal secretion of 
the ovary, or other glands; but if the second pos- 
tulate is considered, satisfactory proof of the in- 
ternal secretory activity of the mammae will be 
forthcoming, for, as will shortly be seen, the an- 
tagonistic relation between the mammae and the 
ovaries is made good use of as the basis of certain 
therapeutic procedures. 

A consideration of several of the numerous ref- 
erences to the use of extracts of the parenchyma 
of mammary glands as a therapeutic agent seems to 
show conclusively that they possess a decided 
therapeutic influence and at the same time empha- 
sizes the importance of what must still be called a 
much neglected field of therapeutics. As a matter 
of fact I am sure that ''hormone therapy," as I 
like to call it, is neither studied nor practiced as 
much as it deserves; and those who will take the 
time to investigate the scientific use of organo- 
therapeutic extracts will quickly find that the as- 
tonishing results accredited to thyroid, adrenal or 
pituitary medication are by no means limited to 
these few; but that a vast territory will be opened 



204 THE INTERNAL SECRETIONS 

up in which will be found many proved and, later, 
more as yet unproved, means which will facilitate 
the solution of many a therapeutic puzzle. 

Mammary extract is produced from the care- 
fully dissected parenchyma of the udders of cows, 
goats or ewes, and is prepared with the precautions 
customary in the manufacture of effective organo- 
therapeutic extracts. It is obtainable in dry form 
or in solution (in ampules). Injections of the lat- 
ter seem to be somewhat painful and, so far as I 
can see, have no special advantage over the powder 
or tablets given by mouth, as in many cases the 
results are just as evident following treatment by 
the internal as by the hypodermic or intramuscu- 
lar method, tending to prove that whatever the 
principle may be that is the cause of the therapeutic 
activity of this extract, it is not destroyed when 
passing through the stomach. 

As we have already seen, there is a decided an- 
tagonism between the mammae and the ovaries, 
and this fact is the basis for the principal use of 
mammary extract. It is used to overcome the re- 
sults of excessive ovarian activity. Among the 
conditions, which have been classed under this head 
are menorrhagia with increased uterine congestion, 
uterine hypertrophy and fibroid degeneration, as 
well as certain conditions in which there is an in- 
creased degree of ovarian activity. The chief 
every-day indications for mammary therapy are 
functional uterine hemorrhages and fibroids. 



IN PRACTICAL MEDICINE 205 

A number of investigators have used this method 
to produce uterine depletion and to control hemor- 
rhages shown to be due to functional causes as 
distinguished from those of organic origin, such 
as the presence of foreign bodies in the uterus, 
polypi, placental remains, cancer, etc. Clearly 
medicinal therapy is not likely to be very effective 
in such conditions as these latter, where the re- 
moval of the foreign body or growth is the most 
reasonable procedure. However, mammary extract 
has been used in the post-operative treatment of 
such cases, especially when there has been a ten- 
dency to protracted oozing. 

Pochon has used mammary substance and re- 
commends it for its decided anti-hemorrhagic in- 
fluence (however, it is not a styptic by any means) 
and calls attention to the fact that while mammary 
extract tends to cause uterine depletion, ovarian 
extracts have an entirely opposite tendency, caus- 
ing an increased uterine blood supply. 

Luncz, in his interesting monograph, has gath- 
ered a number of reports of benign cases in which 
mammary opotherapy caused an entire cessation of 
uterine hemorhrage in persons of widely varying 
age. 

Other writers have gone further, among them 
Forgue and Massabuan, who besides demonstrat- 
ing clinically the anti-hemorrhagic action of this 
preparation, have shown experimentally that at 
the menopause there frequently is an obvious in- 



206 THE INTERNAL SECRETIONS 

crease in the corpora lutea with hypertrophy of 
these cells. They presume that the hemorrhages 
so common at this time may be due to two causes : 
Temporary increased production of the luteal 
hormone, and an associated decrease in the pro- 
duction of its antagonist — the mammary hormone 
— resulting, of course, from the usual retrogressive 
changes expected in the mammae at this period. 
This harmonizes entirely with the facts previously 
collated here, and is further evidence of the sound- 
ness of the position of this form of treatment in 
such cases. 

There are numerous reports showing the anti- 
hemorrhagic influence of mammary substance. I 
have personally prescribed and recommended it in 
a number of cases with good results. Battuaud 
indicates that this form of medication has proved 
valuable in the control of menorrhagia in young 
girls, just as it has been found serviceable in met- 
rorrhagia of the climacteric. Congestive conditions 
of the ovary resulting from inflammation of the 
adnexa and other causes may be reduced in this 
manner, although, of course, the influence is more 
mechanical — i. e., decongestion is brought about 
in a chemical way and there is no particular action 
on the infective process. In other words, mammary 
extract is a valuable adjunct to the specific anti- 
infection treatment, which is now generally recog- 
nized to be the bacterin method. 

Dalche, Jayle, Pozzi and other French gynecolo- 



IN PRACTICAL MEDICINE 207 

gists are convinced of the efficacy of this method, 
while virtually all the references to mammary ther- 
apy in American medical literature are quite a num- 
ber of years old, the chief papers being those of 
Pryor, Crouse and Shober. 

The original application of mammary therapy 
seems to have been made by Robert Bell, of Glas- 
gow, in 1896, and his initial experiences were in the 
treatment of uterine fibroids. He reported before 
the British Gynecological Society four cases, two 
of which were suffering from fibroids, the first in 
a woman of forty-eight, the large fibrous tumor 
being reduced 75 per cent, after four months' treat- 
ment, the menstrual troubles having in the mean- 
time completely disappeared. In the second case 
a smaller fibroma was much reduced in size after 
three months' treatment, the hemorrhage having 
been stopped and the anemia controlled. 

In the last 18 years there have been, perhaps, 180 
cases reported in the literature, the majority of 
them in Russia, although quite a number will be 
found in the French journals. Feodoroff, Professor 
in the University at Petrograd, has made several 
communications on this subject and in his most re- 
cent statistical report refers to a series of 43 women 
treated for fibroids, in 25 of whom the uterus had 
attained the approximate size of the gravid uterus 
at two or three months, in 16 others the tumor be- 
ing larger and corresponding to the gravid uterus 
at four to six months, while in two of them the 



208 THE INTERNAL SECRETIONS 

tumor extended beyond the umbilicus. One-third 
of all these cases was completely cured; in 53 per 
cent, there was a decided reduction in the volume 
of the tumor; in over 80 per cent, the hemorrhage 
was completely stopped, and in 47 per cent, the 
pain commonly noted was relieved. In only 14 per 
cent, of this series was no result whatever secured. 
It is only fair to add that one-half of the complete 
cures were secured in the first series (those in 
whom the volume of the uterus corresponded to the 
pregnant uterus at two or three months) and that 
in the two extraordinarily large tumors no result 
was obtained. These figures, apart from the re- 
ports of several other writers, would almost seem 
to be convincing evidence of the value of mam- 
mary substance in therapeutics, for despite the fact 
that Feodoroff's name is strange in this country, he 
is a very well known gynecologist in Russia. 

Another Russian investigator, Mekerttschiantz, 
is more enthusiastic in his praise of this method, 
and goes so far as to call mammary extract "the 
touchstone for all cases of uterine fibroids"; and 
rightly suggests that it be given a thorough trial 
for several months before operative measures are 
decided upon. (This, at least, is a fair presump- 
tion, for, in my opinion, the surgeon is not always 
justified in performing hysterectomy or pan-hys- 
terectomy until every reasonable medical proced- 
ure has been thoroughly tried without avail.) He 
calls attention to the fact that uterine contractions 



IN PRACTICAL MEDICINE 209 

may be caused by this method, and also believes 
that the retrogressive changes that are brought 
about in interstitial fibroids are due to their trans- 
formation into subserous fibroids v^hich later be- 
come pediculated and are either cast off or ab- 
sorbed. 

In all of his 50 or more cases, Mekerttschiantz 
secured benefit, the hemorrhage was controlled in 
all, the tumor reduced to a minimum in two-thirds, 
and a noticeable betterment in general health was 
remarked. It is interesting to note that in cases 
of fibroid complicated with pregnancy, mammary 
therapy exercises a maximum influence on the ret- 
rogression of the tumor, because the effect of the 
extract is amplified by the increasd mammary ac- 
tivity resulting from the normal physiologic stim- 
uli, as well as by the homostimulation* which is 
also brought about. 

Naturally in all organic diseases the possibilities 
for success in therapeutics are considerably less 
than in functional disorders, hence it must not be 
expected that the application of this method of 
treating fibroids is going to be nearly as effective 
as in the treatment of the less serious and more 
easily controlled functional disorders. In other 
words, functional menorrhagia responds to mam- 
mary therapy much more readily than do uterine 



♦"Homostimulation" is a term coined by Hallion of Paris 
to designate a uniform property of organotherapeutic extracts 
which is summarized in what is now called "Hallion's Law" (See 
page 3.) 



210 THE INTERNAL SECRETIONS 

fibroids; and in the treatment of the latter the 
hemorrhage and other symptoms likely will be in- 
fluenced more and earlier than the tumor itself. 

While the use of mammary extract in therapeu- 
tics has not yet reached the same unassailable posi- 
tion that has been attained by certain other glandu 
lar extracts, notably thyroid, pituitary and adrenal, 
it is none the less a useful procedure for the gyne- 
cologist and the general practitioner; and while the 
experiences outHned previously may not be always 
dupHcated in their entirety, there can be no doubt 
that it is an effective method and that it deserves, 
like many other phases of practical hormone ther- 
apy, more fully outlined in my book of that name, 
to be raised from the obscurity in which it is at 
present involved. 

It is not as difficult to secure effective mammary 
preparations as has been hinted by many with 
whom I have spoken or corresponded. In every 
country that I have visited I have been able to find 
useful preparations and no harm can come from 
referring to some of these. In England one can 
quickly secure Mamos (B., W. & Co.), Ovomam- 
moid Comp. and the Russian product, Mamminum. 
In France there are at least 12 "extraits mam- 
maires," those of Carrion, Choay and Chaix of 
Paris ranking among the best. In this country one 
can usually secure the products named above, as 
well as Mammary Substance (Armour & Co.) and 
Mammogen (G. W. Carnrick Co.), and most of my 



IN PRACTICAL MEDICINE 211 

more recent personal experiences have been lim- 
ited to these latter. 

Before closing, a few words may be said regard- 
ing dosage. It is usually advisable to give 5 or 6 
grains t. i. d. Larger doses may be given, as much 
as 15 or 20 grains at a dose. (Attention is called 
to the fact that not every tablet contains the amount 
of actual substance that corresponds to the weight 
of the tablet, the amount varying with the products 
of different manufacturers.) It seems best to give 
mammary extract just before meals, for in occa- 
sional cases there is a slight tendency to digestive 
derangement following its use. In fact, rarely a 
case will be found in which it is necessary to dis- 
continue the use of this preparation and to re-estab- 
lish the dosage in very gradual steps, commencing 
with one or two grains a day and increasing as 
rapidly as is consistent with the circumstances. 

Obviously in the treatment of conditions of long 
standing this method must be continued over a 
long period, and Battuaud in recommending 0.5 
Gram (7^ grains) of the active substance twice 
a day, suggests that when attempting to control 
hemorhrage between the periods the above dose 
should be continued daily and doubled during the 
hemorrhage. It has been suggested that mammary 
extract should not be given during the menses, but 
I have not found this so. After all, each patient is 
a law unto herself, and, as with many other thera- 
peutic procedures, the best dose is "enough." 



XVII 

CONNECTING LINKS BETWEEN ENDO- 
CRINOLOGY AND OTO-RHINOLOGY 

ON first thought the connection between the in- 
ternal secretory organs and the ear, nose and 
throat is not particularly intimate and, perhaps, 
some of you have felt that the hour this evening 
might be ill-spent in listening to what I have to 
say. If so, I hope that you may be pleasantly dis- 
appointed, for I believe that the connection be- 
tween these two branches of medicine is just as 
evident and as important as those well-defined 
links between other systems or organs of the body 
which have become better known as our knowledge 
of the hormones has increased. 

For the sake of convenience I have divided my 
remarks into two parts, in the first of which I hope 
to show that a well-marked and fundamental rela- 
tionship exists between certain of the glands of in- 
ternal secretion and some of the disorders in your 
special field and vice versa; and in the second, 
briefly to consider several profitable phases of or- 
ganotherapy which specialists such as yourselves 
may apply quite frequently. 

Naturally the thyroid gland would be the first 
to engage our attention, for it is among the most 



An address read before the Eye, Ear, Nose and Throat Sec- 
tion, Los Angeles County Medical Association, May 1, 1916, and 
published in The Laryngoscope (St. Louis), August, 1916. 

(212) 



IN PRACTICAL MEDICINE 213 

important of the hormone-bearing organs. The 
thyroid gland exerts the same influence upon the 
control of the metaboHsm in the cells of the struc- 
tures constituting your province of medicine, as it 
does in the maintenance of cell nutrition and de- 
toxication in any other part of the body. The great 
principle involved in the relation of thyroid insuffi- 
ciency and the condition of cellular infiltration to 
v^hich extended reference was made when I re- 
cently addressed the Los Angeles County Medical 
Society, is responsible for at least a part of the 
troubles which you are called upon to treat. Her- 
toghe himself mentions the frequency with which 
hypothyroidism is associated with noises in the 
ears and dizziness; and even Meniere's syndrome 
may result from this condition of infiltration which 
Hertoghe was the first to direct to the attention of 
the profession some twenty years ago. 

I have encountered several cases of Eustachian 
infiltration with a degree of deafness which was at 
least partially due to this disorder, which cleared 
up when the quite generalized infiltration was rec- 
ognized and its relation to thyroid inadequacy made 
the basis of the only proper treatment — suitable 
thyroid medication. It may not be out of place, 
then, if I should suggest that any of the intract- 
able aural or nasal conditions in which a mucosal 
or more deep-seated infiltration might be present, 
should be a signal to you to search for other evi- 
dences of thyroid disorder. In case any of them 



214 THE INTERNAL SECRETIONS 

are discovered, and you will recall that they are 
not hard to identify, suitable organotherapy profit- 
ably may be made a part of your treatment. I am 
not saying that thyroid extract is a panacea for in- 
tractable nose and throat disorders or that it is the 
rational remedy for noises in the ears or deafness. 
I merely suggest that if any of these symptoms 
serves to direct your attention to an obscure thy- 
roid trouble and you verify it by discovering other 
symptoms usually expected in this quite common 
disorder, it is rational therapeutics and profitable 
therapeutics, too, to exhibit thyroid; and the re- 
sults will be sufficiently good in some cases to make 
up for the failures in others and at the same time 
to convert one to the importance of the diagnostic 
and therapeutic value of this suggestion. 

It should not be necessary to remind you that 
adenoids are almost invariably found in hypothy- 
roid children, so much so that it is now believed 
that this relation is not merely incidental, but that 
the thyroid dyscrasia may have some causative in- 
fluence in the production of the abnormal growths. 
This being the case, it seems to be proper when 
studying adenoid children to look carefully for 
other evidences of thyroid insufficiency and, when 
they are found, to treat them simultaneously with 
the adenoids. With the risk of causing some sHght 
offense by attempting to discuss a subject with 
which I am not very familiar, I will venture the 
statement that it is not good practice to treat an 



IN PRACTICAL MEDICINE 215 

adenoid case by the mere physical removal of the 
offending tissue, while the results of its presence, 
as well as the possible causative factors, still re- 
main more or less definitely present. While aden- 
ectomy undoubtedly gives Nature a better chance 
to reassert herself, which she practically always 
makes the best use of, I believe that suitable or- 
gano-therapeutic and other measures will give her 
a still better chance if an insidious thyroid dys- 
crasia happens to be present. 

We shall not have time to enter into a study of 
the broad subject of the ductless glandular dis- 
orders in that large class of cases which McCready, 
of Pittsburgh, chooses to call "children requiring 
special attention"; but it must be admitted that the 
first one to have an opportunity to investigate such 
cases is the oto-rhinologist, for the most marked 
and obvious disturbance calls for your service. Too 
often this service, usually operative, is all that is 
given and it is unfortunate. One should treat the 
whole child and not merely that disorder which 
obtrudes itself upon the parent, the teacher or the 
family physician. 

I have directed your attention to a few of the 
conditions in the nose and throat which may be 
connected with hypothyroidism and before I get 
away from the thyroid gland, there is another 
phase of its study that has recently been empha- 
sized. Naso-tonsillar infections are a common 
cause of thyroid dyscrasias. Those who have the 



216 THE INTERNAL SECRETIONS 

opportunity of studying many cases of goiter, both 
the so-called ''simple" type and more especially the 
"exophthalmic" type, are beginning to realize that 
overlooked infections of the mouth, nose or tonsils 
are closely connected with the incidence of these 
thyroid disorders. Some reports of work done at 
the University of Wisconsin are very interesting. 
Evans, Middleton and Smith (1) examined the 
mouth, nose and tonsils of three hundred and sixty- 
two individuals with goiter. In no less than 22 per 
cent, of these there was a tonsillar endamebiasis, 
while a less marked but indubitable infection of 
other parts of the mouth and nose was present in 
a much larger number. The importance of this 
was proved by the treatment of a number of the 
cases in which there was a well-marked thyroid 
dyscrasia as well as a goiter, and out of twenty- 
three patients treated with emetine the dysthyroid- 
ism was favorably modified in eighteen cases. 

So just as certain common symptoms that have 
been mentioned lead us to think of thyroid inade- 
quacy as an etiologic factor in nose and throat dis- 
orders, so nose and throat disease may be a cause 
of well-marked thyroid troubles. The inter-relation 
is closer than has been imagined. 

So far as the application of various phases of 
organotherapy in oto-rhinology is concerned, we 
have already mentioned some indications for thy- 
roid therapy. Certainly it is worth applying in some 
of the old, difficult cases in which one can demon- 



IN PRACTICAL MEDICINE 217 

strate a more or less well-marked hypothyroidism. 
I need not tell you of the value of adrenalin, but 
perhaps not many of you have yet had recourse to 
some other organotherapeutic measures for the 
prevention of post-operative hemorrhage, especi- 
ally in nose and throat surgery. The first is the 
intramuscular injection of pituitary solution as a 
means of preventing anticipated bleeding. Kahn, 
in one of your special journals, (2) states that he 
gives twelve minims of the standard solution of the 
posterior pituitary principle fifteen minutes before 
anesthesia is commenced prior to nose or throat 
surgery. The above dose is for children, fifteen 
minims or more may be given to adults. The coag- 
ulation time is reduced one-third to one-half and 
hemorrhage is greatly reduced, especially follow- 
ing turbinate operations. The cardio-stimulant in- 
fluence should be also of much value. 

The second anti-hemorrhagic remedy is pre- 
pared from brain tissue and has been named throm- 
boplastin or kephalin and is used locally, being- 
swabbed on the cut surface. It has been extensively 
used by certain clinicians and further information 
may be found in the writings of Hess (3) and Cro- 
nin. (4) 

Another interesting and not very well studied 
phase of organotherapy is the use of lymphatic 
gland extract in adenoid children. I am not setting 
this forward as something so valuable that it should 
not be missed, rather I am relating an experience 



218 THE INTERNAL SECRETIONS 

which seems to hold within it something of ulti- 
mate clinical value. If the experiences which fol- 
low are worked out — and there are opportunities 
galore for such investigative work — it may be that 
some new and illuminating information may be had 
on the adenoid-tonsil question. Ashby, (5) of Liv- 
erpool, has suggested that the uniform enlarge- 
ment of the tonsils and especially the growth of 
adenoid tissue in children at a fairly constant age 
may be a defensive act of the body, the increased 
tissue being an attempt on the part of Nature to 
supply some secretion or substance which is espe- 
cially needed at this time when adenoid hyper- 
trophy is most usual. The obvious deduction was 
that it might be possible to give this to the body 
just as the missing thyroid, ovarian or pituitary 
substance is of therapeutic efficacy in conditions of 
corresponding glandular insufficiency. So Ashby 
gave thirty children one gram of desiccated lym- 
phatic gland each day for a number of weeks. There 
was obvious improvement, the hypertrophy was re- 
duced, snoring ceased and noises during breathing 
disappeared. This is but a preHminary report and 
is surely deserving of further study, for the oppor- 
tunities are so numerous and the possibilities quite 
considerable. 

Your secretary reminded me to be sure to include 
something of interest to the ophthalmologists, and 
before closing, a word or two of posible interest to 
them may be added. Several important eye condi- 



IN PRACTICAL MEDICINE 219 

tions may be connected with ductless glandular 
disorder. One of them is not yet well differenti- 
ated for it is in the long category of troubles either 
due to or associated with hypothyroidism or, more 
probably, pluriglandular insufficiency. It consists 
of a fairly well defined asthenopia of obscure origin 
with a train of symptoms which is doubtless famil- 
iar to you with muscle weakness predominating. 
This is not an uncommon condition, and when the 
progressively decreasing powers of vision are not 
directly connected with a reasonable cause, and, for 
that matter, even when a cause is quite well de- 
fined, it is well to look for other symptoms such as 
those previously mentioned as being due to thyroid 
inadequacy. In such cases carefully graduated thy- 
roid mediation may be of quite considerable help. 

I need but mention in passing the eye findings in 
exophthalmic goiter, a typical internal secretory 
dyscrasia, the treatment of which is usually out of 
the province of the ophthalmologist. 

One of the most interesting ocular disorders is 
the bitemporal hemianopsia now known to be due 
to pituitary disease. Not uncommonly the oph- 
thalmologist is the first to meet these cases, for the 
sudden or progressive visual disabilities naturally 
call for his aid first. It may be well to outline in 
all brevity the eye symptoms of well-marked pitu- 
itary disease. The enlarged gland in its sellar cup 
causes fairly uniform neighborhood symptoms — 
we are not now interested in which part of the 



220 THE INTERNAL SECRETIONS 

gland may be involved, nor what type of patholog- 
ical changes may be present and what varying se- 
cretory dyscrasias result therefrom — and the chief 
among them affect the sight. The first of these is 
due to the direct pressure upon the optic chiasm 
with either primary optic atrophy (I think this 
term is incorrect as we may shortly see) or, more 
usually, bitemporal hemianopsia. This blindness 
varies in degree and rapidity of onset, but more 
often first affects the visual acuity for colors only, 
and later for form as well. Professor Gushing very 
kindly sent me last week a valuable monograph by 
himself and C. B. Walker, (6) in which the distor- 
tions of the visual field from brain tumors are in- 
terestingly considered. The conclusion of this 
study is worth reiterating: Detailed perimetry with 
small test objects of several sizes is advocated for 
patients with pituitary disease in order that stages 
of hemianopsia antecedent to those usually recog- 
nized may be detected. 

The other eye symptoms are found in more 
marked cases, i. e., when the pituitary tumor ex- 
tends beyond the sellar edges. In such cases there 
may be paralysis of both of the external recti with 
resulting internal strabismus due to pressure on the 
sixth cranial nerve, or by similar pressure on the 
third cranial nerve external strabismus may result. 
Still later the increased intracranial pressure will 
cause choked disc and ultimate total blindness. 
This condition and the so-called ''primary optic 



IN PRACTICAL MEDICINE 221 

atrophy" (of pituitary origin) or descending at- 
rophy does not necessarily mean an anatomical de- 
generation of the nerves, but according to Gushing 
(loc. cit.) it is very often only a "physiological 
block to the transmission of the visual impulses" 
w^hich may be relieved speedily by decompression 
or other more serious surgical measures. 

As in all other phases of medical endeavor the 
ramifications of the internal secretory threads are 
closely intertwined w^ith every phase of physiolog- 
ical activity and as the skein is unravelled and our 
understanding of these interrelations becomes more 
comprehensive, there comes a better control of 
many conditions, the treatment of which has been 
beset previously with seemingly insurmountable 
difficulties. Enthusiasm in the study of the inter- 
nal secretory organs and their disorders is not to 
be scorned, for it leads one into fields in which 
many of the flowers "born to blush unseen and 
waste their sweetness on the desert air" may be 
viewed, handled and appreciated as never before. 

REFERENCES 

1. Evans, Middleton and Smith: Amer. Jour. Med. 
Sciences, February, 1916 cli, p. 210. 

2. Kahn : Ann. Otol., Rhinol. and Laryngol., June, 
1915. 

3. Hess: Jour. Amer. Med. Assn., April 24, 1915, 
p. 1395. 

4. Cronin : Ibid., February 19, 1916, p. 557. 

5. Ashby: British Med. Jour., 1913, i, p. 1159. 

6. Cushing and Walker: Brain, March, 1915, xxxvii, 
p. 341, 



XVIII 

THE TREATMENT OF RICKETS 

RICKETS is a nutritional disorder of children, a 
form of starvation, hence before it can be treated 
effectively we must know what factors are promi- 
nent in the production of the disturbed metabolism 
and what elements can be given acceptably to re- 
place those that are deficient. From an experi- 
mental standpoint, rickets is now understood to be 
a result of endocrine disorder. It has been pro- 
duced more easily and quickly by the removal or 
destruction of certain of the glands of internal se- 
cretion than by dietetic restriction. In fact, the 
dietetic element in the etiology of rickets seems to 
be losing a good share of the importance that was 
until recently attributed to it. 

Direct medication. Five things need to be ac- 
complished: 

1. Replace the missing mineral element in the 
blood and bones — calcium. The best calcium salt 
is the phospate, which is conveniently given in the 
U. S. P. syrup of calcium lactophosphate, two 
drams, three to six times a day. 

2. Replace the missing vitamines, factors which 
are now being recognized as playing an important 
part in many nutritional disorders. In nursing chil- 



Prize Question No. CLXVII, for which a prize of $25.00 
was received from the editors of the New York Medical Journal. 
Published in the N. Y. Med. Jour. April 1, 1916. (Copyright 
1916 by A. R. Elliott Publishing Company.) 

(222) 



IN PRACTICAL MEDICINE 223 

dren with serious malnutrition it is often noted that 
the mother is badly nourished, and suitable treat- 
ment will augment the value of her milk. In thera- 
peutics this is accomplished by suitable dietetic reg- 
ulation and by organotherapy. 

3. Antagonize a tendency to acidosis which is 
invariably present in rhachitic children and is quite 
frequently overlooked. Sodium citrate is excellent 
for this purpose and, incidentally, when given with 
milk, it prevents the formation of large curds and 
thus favors digestion. When the urinary acidity is 
high, sodium bicarbonate may be given in small and 
frequent doses, well diluted and so timed as not to 
interfere with digestion; though the citrate has an 
almost equal neutralizing value. 

4. Enhance the mineral content of the blood. In 
addition to the calcium salts we can advantage- 
ously give the salts secured from fresh vegetables. 
This is an extremely important part of the suc- 
cessful treatment of rickets, for these saline ele- 
ments seem to be urgently needed by the system; 
and are easily prepared and assimilated. In France 
bone substance is used not uncommonly and per- 
haps there is some advantage in this organic form 
of calcium. Until recently preparations of bone 
(not bone marrow) were difficult to secure but Rus- 
sell of New York has lately produced a prepara- 
tion of green bone which should be as much better 
than the powdered bone as it is better than the 
ordinary mineral salts we usually prescribe. 



224 THE INTERNAL SECRETIONS 

5. Favor the restoration of the conditions which 
cause or aggravate the disturbed mineral metabo- 
lism. This is best accomplished by suitable organo- 
therapy. Many times small doses of thyroid ex- 
tract — one quarter to one half grain, three times a 
day — will influence the nutrition of the rhachitic 
child in a most decided manner. Thymus extract 
has been recommended upon the theoretical ground 
that the thymus controls calcium metabolism and 
that rickets is possibly a manifestation of hypo- 
thymism, for a characteristic result of thymectomy 
in young animals is a typical rickets with marked 
softening and bending of the long bones, especially 
of the legs; and many autopsies of children dying 
with rickets show the thymus to be atrophied pre- 
maturely. Again, pituitary is occasionally recom- 
mended, while total adrenal substance has facili- 
tated recovery after other measures had been tried 
with little or no benefit. 

The stimulation of the endocrine glands is a 
matter of special importance, as unless this is done 
the calcium salts given simultaneously may be ex- 
creted and thus be useless, for it is certain that the 
fundamental factor in rickets is not so much a de- 
ficiency of calcium as an inability to fix and utilize 
it. This capacity is undoubtedly under the control 
of the ductless glands, those just mentioned being 
the most important. 

Pluriglandular therapy is a useful even if empiric 
procedure in rickets. The following combination is 



IN PRACTICAL MEDICINE 225 

well worth trying: 

Total adrenal substance... 2 parts ; 

Desiccated thyroids 1 part; 

Thymus gland 3 parts ; 

Excipient to make 10 parts. 

Two or more grains of this mixture, depending 
upon the age of the child, may be given three times 
a day. The proportions may be varied, or pituitary 
substance (total) may replace one part of the ex- 
cipient. A total of one and a half to two grains 
each of thyroid and adrenal, and ten grains of 
thymus may be given in twenty-four hours. Car- 
pani (Lancet, June 19, 1915) recommends pluri- 
glandular therapy in rickets and gives powdered 
and dried gland substances in toto, in doses suitable 
to the age, in milk, for fifty days, omitting this for 
one week after the first month's treatment. He 
noticed rapid and striking improvement, especially 
early in the treatment, the benefit first noticed in 
the digestion, then in the nervous manifestations, 
and later in the blood and osseous system. 

Another form of organotherapy which is quite 
generally used, is the administration of codliver oil 
alone or in various forms and combinations. The 
benefit is not due merely to the easily assimilated 
hydrocarbons, but also to the vitamines which are 
present and to a substance of a hormone nature 
which apparently aids in the metabolism of lime 
salts. Parenthetically it may be remarked that 
these substances are present in greater quantities in 
the cruder products, thus explaining the statements 



226 THE INTERNAL SECRETIONS 

of Leonard Williams and others to the effect that 
the cruder the oil, the better its therapeutic effects 
in many cases. 

Hygienic care. Obviously the general care of 
rhachitic children should be as good as possible. 
Good hygiene favors all treatment, and usually chil- 
dren suffering with rickets have not had the home 
care they needed. The emunctories must be watched 
and regulated by the diet, by an occasional dose of 
castor oil, and, at the beginning of the treatment, by 
calomel in divided doses. The skin and circulation 
should be stimulated by daily cool bathing with 
friction. Sodium bicarbonate in the water (a heap- 
ing teaspoonful to each quart) is often an advan- 
tage, especially where the skin is chafed. Gentle 
massage with almond or olive oil is valuable. Sun- 
shine, fresh air, suitable exercise, and regular rest 
are all important, especially the first two. 

Dietetic management. Most rhachitic children 
have been poorly fed and the malnutrition is not 
confined to the bones. Digestion is poor and assim- 
ilation is reduced. Fresh milk, because of its rich- 
ness in vitamines and ''living salts," is by far the 
best food. Pasteurized milk is a poor substitute, 
prepared foods are usually unsatisfactory, and 
boiled milk is the worst food that could be selected. 
The value of sodium citrate has already been men- 
tioned, and lime water is also useful in modifying 
the milk. Limits of space forbid a discussion of 
the necessary milk modification and its administra- 



IN PRACTICAL MEDICINE 227 

tion. Suffice it to say that the child must be fed 
with milk modified on the basis of its weight, not 
its age — at least until digestion is normal and the 
child is obviously improving. At this stage barley 
gruel, oatmeal gruel, corn flakes, and other "heav- 
ier" cereal foods may be added, and later potatoes 
(baked) and other foods as a tolerance for them is 
established. 

Between meals plenty of fluid should be given, 
and it should be planned to carry in this as many of 
the assimilable, vegetable mineral salts as conve- 
niently can be given. Small quantities of fruit 
juices, especially orange and prune, may be given 
two or more times a day. Often idiosyncrasies to 
these are found, hence the need for caution. 

Another excellent dietetic adjuvant, I might bet- 
ter say therapeutic measure, is clear vegetable soup. 
Sometimes it may accomplish more than any of the 
direct remedies mentioned previously, since it con- 
tains Nature's minerals, which normally form the 
inorganic pabulum of the cells. The preparation of 
this soup is important, and, incidentally, it will be 
found a most valuable remedy in many metabolic 
dyscrasias in adults as well as children, including 
rheumatism, malnutrition, certain neurasthenic 
conditions, etc. 

Spinach, potatoes (or well cleaned potato par- 
ings), carrots, turnips, fresh peas (with the pods), 
and, perhaps, small amounts of onions, are washed, 
cut up, and covered with two or three times their 



228 THE INTERNAL SECRETIONS 

volume of water. Raw wheat or bran may take the 
place of one or more of these vegetables, if desired. 
The exact ingredients or their relative amounts are 
not of such great moment. Simmer for three or 
more hours over a slow fire, or, better still, boil 
briskly for fifteen minutes and place in a fireless 
cooker for three to five hours. Strain without pres- 
sure. The remainder may be passed through a sieve 
and used as a basis for a palatable thick soup for 
the table. One to four ounces of this clear liquid 
may be given four times a day, with or between the 
feedings. Bran water may be used. It is pre- 
pared and given in approximately the same way. 

The surgical care of deformed bones is a matter 
for the attention and care of the orthopedist. 
Braces may be helpful, osteoclasis is often advis- 
able; but in any event the foregoing suggested out- 
lines for the treatment must be associated with sur- 
gical care. 



XIX 

THE ORAL ADMINISTRATION OF 
ADRENALIN 

THE active chemical entity prepared from the 
adrenal medulla is oxidized and destroyed very 
easily in the body. This accounts for the ephemeral 
effects which follov^ its administration as a remedy; 
and also the comparative rarity of the symptom 
complex of hyperadrenia. In vitro adrenalin is 
quickly destroyed by numerous reagents and it has 
also been shown that it loses its activity when in 
contact for a short time with the gastric juice. If 
adrenalin is given by mouth, and the stomach is 
evacuated ten minutes later, it is usually impos- 
sible to detect this substance. In the fasting stom- 
ach this disintegration is accomplished in almost 
the same time, though here the writer is by no 
means sure that this really means that the adren- 
alin is destroyed, for some of it is absorbed. 

All these experiences have led to a quite natural 
impression that adrenalin was not effective when 
given by mouth, and that to obtain other than the 
well known results, it must be given by hypodermic 
or intravenous injection. There are not a few ref- 
erences in medical literature, including that of the 
manufacturers, which indicate that this idea is well 
grounded in the minds of the profession. 



Reprinted from the New York Medical Journal, November 
4, 1916. (Copyright, 1916, by A. R. Elliott Publishing Com- 
pany. ) 

(229) 



230 THE INTERNAL SECRETIONS 

For years I have been convinced by personal ex- 
periences that this opinion was misleading, and am 
confident that unquestioned therapeutic effects 
have follow^ed the oral administration of adrenalin. 

In a short commimication to the editors of the 
New York Medical Journal (July 8, 1916, p. 94) 
Leland Boogher relates some interesting personal 
experiences following the use of fifteen minims of 
adrenalin solution (presumably the standard one in 
1,000 solution) in a tablespoonful of water by 
mouth for the relief of excruciating abdominal pain 
due to an abscess in the transverse colon. Boogher 
has since recommended this measure as an anal- 
gesic remedy for gallstone and renal colic, and ''it 
gave splendid relief." This reference emphasizes 
what is probably an original application of this 
much used remedy; and credit for this should be 
given to Dr. George Richter, of St. Louis, who pre- 
scribed the treatment outlined above. 

However, this experience is also corroborative 
evidence of a well established fact, still denied in 
many quarters, that adrenalin per os is both potent 
and useful. In American Medicine a number of 
items have been reported which substantiate this 
view. In the issue for April, 1915 (p. 253), there 
appears an article entitled "Giving Organothera- 
peutic Products by Mouth," by the writer, in which 
reference is made to the prevalent but mistaken no- 
tion as to the availability of many organothera- 
peutic extracts when given per os. Reference was 



IN PRACTICAL MEDICINE 231 

there made to a statement to the effect that "these 
(organotherapeiitic) extracts, with the possible ex- 
ception of thyroid, are destroyed in the stomach; 
hence it is useless to give them unless hypodermic- 
ally." The writer then proceeded in the following 
terms: "This is not true, and the statement can 
be easily disproved. . . . Why, if organothera- 
peutic remedies generally are destroyed by the di- 
gestive juices, should thyroid be the lone exception 
to the rule? Wherein does the active principle of 
the thyroid differ in its absorbability or destructi- 
bility from the hormones of the adrenals, pituitary, 
or gonads? The most conclusive and practical 
proof of the inaccuracy of such a position would 
be to have those who make such statements (or be- 
lieve them) take, say, an ounce of one in 1,000 ad- 
renalin chloride solution — it contains less than half 
a grain of the active principle — and note carefully 
if there is not a considerable modification of the cir- 
culatory equilibrium!" 

Several of the statements as to the destructibility 
of adrenalin when given by mouth appear in the 
scientific publications of the American Medical As- 
sociation, though, curiously enough, in the weekly 
department on Therapeutics in the Journal A. M. 
A. (October 16, 1915, p. 1366) there is a brief con- 
sideration of the emergency treatment of sudden 
cardiac failure from which the following statement 
is cited: "Epinephrine may be given in a dose of 
five drops on the tongue, which may be repeated in 



232 THE INTERNAL SECRETIONS 

half an hour if advisable. . . . All of the fore- 
going (including strychnine, hot coffee, camphor, 
etc.) are quick acting treatments.'' This casual 
statement is of unusual interest, since the use of 
epinephrine (which, by the way, is not obtainable 
on prescription, as there is no such preparation on 
the market, but is presumably intended to mean 
adrenalin) is advised to be given by the mouth, 
contradicting statements in the Journal A. M. A. 
and elsewhere which indicate that this drug is use- 
less given in this manner; and here, be it noted, 
this remedy, in a dose of only five drops on the 
tongue, is classed as a "quick acting" cardiac stim- 
ulant. 

There are a number of other references to the 
effective administration of adrenalin by mouth, a 
few of which will be referred to shortly. It should 
be understood, however, that such fundamental er- 
rors as the one under discussion are due to the 
drawing of conclusions from laboratory experi- 
ments alone. We grant that adrenalin is "digested" 
in the test tube. It is easy to prove that it cannot 
be recovered from the gastric contents after being 
in the stomach for only a short time. None will 
deny that it is rapidly and thoroughly oxidized. But 
adrenalin is also very easily absorbed, as every 
rhinologist knows and as any physician can quickly 
find out if he cares to hold a dram or two in his 
mouth for a few minutes. Is it not possible, then, 
as the writer suggests, that the factor of destruc- 



IN PRACTICAL MEDICINE 233 

tion in the stomach is not concerned at all, but that 
much or all of the active principle is taken up by 
the mucous membrane of the mouth, palate, esoph- 
agus, and cardia, thus enabling it to exert its thera- 
peutic effects and to maintain its reputation as a 
"quick acting" remedy when given by mouth? 

In connection herewith it should be recalled that 
the administration of hormones — and adrenalin is 
certainly a hormone and has been quite properly 
called the ''chromaffin hormone" — brings about 
physiological effects in two ways : First, by the di- 
rect action of that part of the actual substance ad- 
ministered; and, second, by the increased produc- 
tion by the organism of the hormone correspond- 
ing to that which is given. In other words, when 
we give adrenalin, not only do we get the direct 
drug effect from the dose which is absorbed, but at 
the same time we are increasing the capacity of the 
adrenal medulla to produce more of its chromaffin 
hormone. 

We know, from many experiences with thyroid 
therapy, that with a presumably normal or even a 
slightly deficient thyroid, certain doses of thyroid 
extract will bring about symptoms of hyperthy- 
roidism the results of which are not directly due to 
the drug administered, but to the increased thyroid 
activity, and these results remain long after the 
comparatively small amounts of thyroid which 
were given have been used up. This shows that the 
principle of homostimulation applies to normal as 



234 THE INTERNAL SECRETIONS 

well as disordered glands, and this is just as pos- 
sible with the adrenals as with the thyroid. 

To lend emphasis to the position taken by the 
writer, as well as to Boogher's brief but interesting 
communication, a few clinical reports from recent 
literature may be collated here with advantage: 

Hutinel (Arch, de med. des enfants, February 
and March, 1915) recommends three or four drops 
of adrenalin solution one in 1,000, diluted, every 
two or three hours, as a part of the treatment of 
severe infectious diseases in children. Each child 
may receive as much as twenty minims a day by 
mouth, and Hutinel remarks that he has never ob- 
tained so much benefit from the usual supporting 
measures and that the effects are remarkable even 
in the gravest cases, since the blood pressure is in- 
creased and there is an immediate response in the 
general mental and physical condition, while the 
pulse rate is reduced and diuresis is favored. 

M. H. Smith (Medical Record, October 2, 1915, 
p. 586) reports having successfully treated several 
cases of Rocky Mountain spotted fever with ten 
drop doses of adrenalin solution every four hours. 
This obviated the prostration common in these 
cases, convalescence was established earlier than 
usual, and there was an apparent beneficial effect 
upon the course of the disease. That the remedy 
given by mouth was "quick acting" is emphasized 
by Smith's remark that within a few minutes of 
the administration of each dose, a fullness of the 



IN PRACTICAL MEDICINE 235 

pulse and a fading of the eruption were noticeable. 

Not much has been done in this country with the 
use of adrenalin for the treatment of nephritis, 
though at least five articles have appeared in cur- 
rent Italian medical literature speaking well of this 
method. The most recent reference is abstracted 
in the Journal A. M. A., June 10, 1916. This ab- 
stract from II Policlinico (April 30, 1916) may be 
cited in full: "Borelli reports two cases of acute 
and one of chronic nephritis in which remarkable 
benefit was realized by epinephrine* treatment. 
One patient was a child of nearly five years, the 
others were men of fifty and sixty-two. He gave 
the child sixteen drops a day of a one in 1,000 solu- 
tion of epinephrine, four drops at four hour inter- 
vale. The adults were given forty drops a day, 
eight at a time. Ercolani called attention, in 1910, 
to the benefit from epinephrine by the mouth in 
nephritis, commending the harmlessness, ease, and 
efificacy of this method of treating kidney disease, 
which has proved its usefulness again and again, 
and Borelli's experience has confirmed this." 

Previous to this report another exhaustive study 
on the subject was published by Silvestri (Gaz. d. 
osp. e d. clin., September 1, 1915), in which he ana- 
lyzes the reports of a number of other clinicians, 
adds several personal experiences, and proves that 



♦"Epinephrine" is the term used uniformly in all the pub- 
lications of the American Medical Association, although in this 
instance the title of Borelli's original article is: "Cura della 
nefrite con la soluzione di adrenalina nella pratica di condotta." 



236 THE INTERNAL SECRETIONS 

adrenalin is a most valuable aid in the acute stages 
of nephritis, but of little value in chronic condi- 
tions. He also tells of the experiences of Fede, who 
found this procedure comparatively more effective 
in children, since in them the elasticity of the renal 
glomeruli and tubules is greater, while the adrenal 
glands are proportionally larger in children than in 
adults (presumably being more susceptible — quan- 
titatively — to the homostimulant action referred to 
previously). Silvestri suggests that 1 or 2 minims 
of the 1 :1000 solution of adrenalin chloride be 
dropped on the tongue every three hours — the total 
amount given being regulated by the clinical re- 
sponse. For adults the dose may be larger. 

There are also numerous reports in the literature 
of the therapeutic efficacy of total adrenal gland, 
and of course this is given per os in tablet form. In 
a recent monograph on "Drug Therapy of Cardio- 
vascular Diseases,'' Satterthwaite (Int. Clinics, 1, 
1916, p. 26) recommends desiccated adrenal gland 
as a useful vasomotor tonic in doses of two and a 
half grains three times a day, and remarks that 
single doses as a rule will relieve palpitation in a 
comparatively short time. The active principle of 
the desiccated gland is naturally similar to that 
which is available in a pure state, and the favorable 
experiences with total adrenal gland therapy, by 
mouth of course, is additional proof that the posi- 
tion of those who have contended that the oral ad- 
ministration of adrenalin is useless, is fallacious. 



XX 

THE ADJUNCT TREATMENT OF 

TUBERCULOSIS WITH CERTAIN ORGANIC 

EXTRACTS 

AS the years go by our ideas regarding the treat- 
ment of tuberculosis are modified, and in no phase 
of therapeutics do opinions change so much. About 
1890 Professor Koch discovered a therapeutic won- 
der in tubercuhn, but its vogue v^as short-Hved, for 
the intricacies of dosage had not then been learned. 
Less than ten years ago hyperalimentation v^as the 
fashion, and, as with fashions in other things, it 
was carried to extremes. Nowadays tuberculin has 
regained its place, but its application is almost an 
obsession, and the devotion of some practitioners 
to tuberculin in one form or another seems to show 
that the fashion has changed again. 

There appears to be an idea, almost universal, 
that as tuberculosis is an invasion of the body by a 
certain bacillus, the treatment must needs be di- 
rected primarily towards the destruction of these 
organisms and the neutralization of their toxic 
products. That this is essential none will deny, 
but, unfortunately, the view is much too narrow. 
Tuberculosis is first and foremost a condition of 
lowered resistance in which the infective process 
has become so prominent as quite to overshadow 



British Journal of Tuberculosis (London), 1913, Vol. vii, 
p. 170. 

(237) 



238 THE INTERNAL SECRETIONS 

the original and by far the most important defect. 
The following extract from a recent editorial (1) 
aptly states the matter in the plainest of language: 

''The cause of active tuberculosis must now be 
sought in something which destroys our tolerance, 
and permits our own lesions to develop. Chief 
among these causes are the acute infections. . . . 
In addition to these infections anything else which 
lowers the general health may thus interfere with 
that constant production of antibodies upon which 
our tolerance depends. We can definitely trace 
many cases to a long period of overwork, alcoholic 
excesses, exposure to wet, or adverse climate con- 
ditions. Indeed, anything which interferes with a 
perfect condition of health may allow the spread 
of a focus of infection which we had carried around 
for a half century or more. Even senility itself may 
do this. Many men carry the pneumococcus in their 
mouths all their lives, only to be killed by it in the 
end; and we must now look upon the tubercle bacil- 
lus in the same light of a constant companion, 
harmless as long as we remain in good condition, 
but a malignant enemy the instant our guards are 
lowered." 

It is admitted that the good results of the hygi- 
enic methods at present in vogue are evidence that 
a general building up and restoring of the vitality 
is needed, but, after all, is not this merely a passive 
form of resistance? Some more active adjunct 
would be welcome, and it is believed that such will 



IN PRACTICAL MEDICINE 239 

be found in a consideration of the internal secre- 
tions as well as of the possibilities of organotherapy 
as an auxiliary method of treatment. 

Arnold Lorand, in his interesting book ''Old Age 
Deferred," points out that when the usual sanato- 
rium treatment is having its good effects there is a 
local disintoxication, and the cells of the lungs are 
co-operating in this process in a manner analogous 
to the internal secretion by the cells of other gland- 
ular structures. This may be one reason for the 
fleeting advocacy by some of extract of lung-tissue 
as a remedy in pulmonary disorders. (2, 3) Lorand 
continues: 

''It is a positive fact that under-nutrition (or de- 
fective nutrition) through lack of the necessary 
amount of proteids in the diet exposes one more to 
infection by the bacilli. . . . The findings of Gra- 
witz indicate that an insuflicient proteid diet pre- 
disposes also to anemia. The importance of this 
fact is emphasized by Sajous, who has shown 
(1903) that defective nutrition weakens the activ- 
ity of the pituitary, thryoid and adrenals, the secre- 
tions of which take an active part in the destruction 
of bacteria and their toxins." (4) 

The usual general manifestations almost invari- 
ably present in cases of tuberculosis — fever, lassi- 
tude, and diminished metabolism — can not but be 
accompanied by disturbances of a similar nature 
in the work of the internal secretory organs. Per- 
haps the importance of these functions, many of 



240 THE INTERNAL SECRETIONS 

which are as yet Httle understood, is even greater 
than we think, and certain facts can bear much 
emphasis and repetition. Professor Schafer, in his 
presidential address before the British Association, 
June, 1912, (5) says: "The second essential condi- 
tion for the maintenance of the life of the cell- 
aggregate is the co-ordination of its parts and the 
due regulation of their activity, so that they may 
work together for the benefit of the whole. . . . 
The activities of the cells constituting our bodies 
are controlled in another way than through the 
nervous system — viz., by chemical agents circulat- 
ing in the blood. . . . These substances have re- 
ceived the general designation of 'hormones,' a 
term introduced by Professor Starling. Their 
action, and indeed their very existence, has only 
been recognized of late years, although the part 
which they play in the physiology of animals ap- 
pears to be only second in importance to that of the 
nervous system itself; indeed, maintenance of life 
may become impossible in the absence of certain of 
these hormones." 

When we consider all the emphasis that has been 
laid upon the importance of the internal secretions, 
it seems strange that their relation to tuberculosis 
is rarely mentioned. Treatment based upon the 
regeneration or regulation of these important 
glandular functions is quite the exception, and will 
continue to be until the importance of their rela- 
tion to the original cause of tuberculosis is realized. 



IN PRACTICAL MEDICINE 241 

Our French colleagues, always more alert in the 
application of measures "on the border-line of 
progress in therapeutics," have for some years been 
emphasizing the importance of "Les Opotherapies 
dans la Tuberculose," and a valuable resume with 
the above title was recently published. (6) In this 
article reference is made to no less than fourteen 
distinct forms of opotherapy, of which perhaps 
only one — the use of red bone-marrow — has found 
any favor in England and America. 

It would seem that the most important phase of 
the organotherapy of tuberculosis is unquestion- 
ably the use of spleno-pancreatic extracts. Next in 
importance is the use of preparations from the liver, 
and the value of these methods is enhanced by the 
administration of secretin — a hormone prepared 
from the pylorus and duodenum. 

With the use of extracts of thyroid, pituitary, ad- 
renal, lung, ovary, and testes, I have had no experi- 
ence, and although numerous references to these 
various subjects can be found in the medical litera- 
ture, especially that of France and Italy, the re- 
mainder of this article will be devoted to brief con- 
sideration of the forms of organotherapy first men- 
tioned the use of the extracts of spleen, pancreas, 
liver, and duodenum. 

Practically every form of organotherapy that is 
recommended in tuberculosis is useful only as it 
influences nutrition, and this is essentially true of 
the use of splenic extract. In an exhaustive paper 



242 THE INTERNAL SECRETIONS 

on the subject, (7) the writer has gathered together 
some information regarding the fundamental func- 
tions of the splenic hormone, and concludes that 
the value of splenic extract in practical therapeu- 
tics may depend on the occurrence of a hormone or 
hormones which are concerned in the defenses of 
the blood in tryptic and intestinal digestion in the 
reparative processes, and in certain specific func- 
tions on the part of the spleen itself. Bayle, of 
Cannes, has obtained results which he regards as 
-almost of a specific nature, and in his paper, read 
before the last International Congress at Rome, (8) 
he concludes : 

"I feel authorized by my results to call splenic 
opotherapy a specific treatment for tuberculosis. It 
is a specific from the therapeutic viewpoint, because 
it modifies the soil, rendering it less suitable as a 
medium for the culture of the bacillus of Koch. It 
is a specific from the practical viewpoint because it 
manifests all the function and rapidity of action of 
a specific medication. Employed in convalescents 
it prevents tuberculosis by increasing the mineral 
content of the tissue (en remineralisant le terrain). 
Employed in confirmed cases of tuberculosis it 
cures them.'' Bayle has recently given a very con- 
cise resume and bibliography of his entire work on 
this subject. (9) 

Schroder, (10, 11) Superintendent of the Neuen 
Heilanstalt fur Lungenkrankheit, Schomberg, 
along with his colleagues there, has made an ex- 



IN PRACTICAL MEDICINE 243 

tensive series of experiments on puppies and guinea- 
pigs, and concludes that the administration of 
spleen extract exercises a powerful influence against 
the progress of inoculation tuberculosis in these 
animals. ''The minimizing effect of the spleen ex- 
tract was obvious, insuring a longer duration of life 
and milder lesions in the animals treated, as com- 
pared with the control animals." 

Van Stockum, (12) of Amsterdam, has carried 
out a series of interesting tests in the treatment of 
tuberculosis with extract of spleen previously ex- 
posed to the X-rays. His report on 3,000 cases so 
treated is convincing evidence that the use of this 
preparation is followed, especially in the surgical 
forms, by an early betterment. He also lays stress 
on the harmlessness of this method. In a recent 
editorial (13) appears a statement which deserves 
emphasis: ''The subject is certainly one that should 
not be lost sight of, and practitioners may well re- 
member that advantage may accrue from the use of 
splenic substance as an adjuvant at any rate." 

Tuberculous patients are invariably sufferers 
from toxemia, not only the specific toxemia, but 
also that due to stagnant digestive functions and 
deficient detoxicating power. We know that the 
successful use of various liver extracts for a num- 
ber of years definitely has proved that they have a 
noticeable detoxicating power, (14) due doubtless 
to the fact that the internal secretion of the liver 
has this property. This is probably the cause of 



244 THE INTERNAL SECRETIONS 

much of the good that has resulted from the use 
of this class of preparations. Lemoine and Gerard 
(15) have brought forward a petroleum extract of 
bile called "paratoxine," which is said to be useful 
in tuberculosis, chiefly on account of its antitoxic 
action. 

In studying this subject, and applying it in their 
extensive clinical work in Paris, Gilbert and Car- 
not (16, 17) found that liver extract possessed an 
antihemorrhagic influence, and they used it in the 
treatment of hemoptysis, especially in tuberculosis, 
with very encouraging results. In cases where tu- 
berculosis is associated with hepatic enlargement 
and derangement this form of organotherapy con- 
fers great benefit. H. Parmentier (18) reports that 
liver extracts have a generally good influence in 
tuberculosis, causing an increase in weight as well 
as a decrease in the night sweats and number of 
bacilli in the sputum. His experiences confirm those 
of Gilbert and Carnot, which proved the value of 
liver preparations in hemoptysis. 

It has been frequently suggested that the thera- 
peutic value of codliver oil is due in considerable 
part, not to the contained fat, but to a certain inter- 
nal secretion of the liver of the cod. This may act 
directly, or, more likely, according to Leonard Wil- 
liams, (19) by stimulating one of the normal in- 
ternal secretory glands, the secretion of the one so 
stimulated being inimical to the development of 
the tubercle bacillus. It is a significant fact, he 



IN PRACTICAL MEDICINE 245 

adds, that the darker and more crude the codliver 
oil the more efficacious it is. 

The pancreas undoubtedly plays an important 
part in defending the body against infection. In 
proof of this one has only to remember the fre- 
quency with which diabetics suffer from boils and 
local infective processes, and the remarkably high 
percentage of diabetics that suft'er and die from 
concomitant tuberculosis. This leads one to belicA^e 
that the pancreas, in addition to its known func- 
tions, plays an important part in regulating resist- 
ance to infection. Brieger (20) has shown that 
pancreatin lowxrs the abnormally high antitryptic 
index of the blood in tuberculosis, and predicts that 
eventually treatment will be on the lines of a com- 
bination of pancreatin and tuberculin. Strubell (21) 
has made the definite statement that pancreatin 
administered per os increases the opsonic index to 
the staphylococcus. This may explain some of the 
encouraging results obtained from spleno-pancre- 
atic-opotherapy in tuberculosis, and also the bene- 
fit to the diabetic which often follows pancreatic 
therapy. Referring to this, the editor of the Medi- 
cal Record (22) says: ''The future may witness the 
routine use of pancreatin in tuberculosis . . . and 
in many chronic affections with lowered opsonic 
index." 

Digestion is almost invariably poor in tubercu- 
losis, and, unfortunately, in no class of disease is 
a vigorous digestion more necessary. The tendency 



246 THE INTERNAL SECRETIONS 

to push the feeding of the consumptive often over- 
taxes digestion, and where hyperalimentation is 
necessary, or where decreased digestive capacity 
has already made itself manifest, secretin is a most 
reasonable and useful remedy. 

As originally shown by Bayliss and Starling, 
secretin is a specific chemical activator of pancre- 
atic function, produced in the duodenal walls. Se- 
cretin actually combines with the precursors of the 
pancreatic digestants and is used up in their forma- 
tion. Other investigators have shown that this in- 
fluence is not confined to the pancreas, but that 
secretin stimulates both the peptic and the oxyntic 
glands of the stomach, as well as those glands 
which produce the succus entericus, and some 
French investigators pointed out that secretin also 
stimulates the liver. Whether the influence of 
secretin is or is not as widespread as has been stated 
above, there can be no doubt that it has a salutary 
influence upon digestion, an influence nowhere 
more essential than in the treatment of tubercu- 
losis. Boardman Reed draws attention to the or- 
ganic derivatives as valuable factors in the treat- 
ment of indigestion, and gives his experiences (23) 
with a preparation called ''secretogen," which con- 
tains gastric and pancreatic secretins and entero- 
kinase, with 0.5 per cent. HCl. It has proved in 
a number of cases to be much more effective than 
the usual pepsin-HCl combinations, rapidly bring- 
ing the stomach up to normal, and improving the 



IN PRACTICAL MEDICINE 247 

intestinal digestion and assimilation. The author 
gives the result of gastric analysis made in one of 
the cases, in which secretogen was suspended for 
a month. The proportions of both free and com- 
bined HCl were found to be still a little above nor- 
mal, though before the remedy was taken there had 
been no free HCl at all, and the proportions of both 
combined HCl and total acidity were below normal. 

The importance of hormones in the treatment of 
disease is daily being more fully recognized, and 
there is little doubt that before long their value as 
an adjunct in the treatment of tuberculosis will be 
generally accepted. The results already published 
admit of no doubt, and are sufficient at least to dis- 
arm skepticism. We have not found a panacea for 
tuberculosis, nor are we likely to find one soon; but 
it can not be gainsaid that the control of the body 
functions as a whole — and especially that control 
aimed at in an attempt to regulate the hormone 
balance — will be eventually a very important factor 
in the successful treatment of tuberculosis. We 
shall do well to bear this in mind, not forgetting 
that "an attitude of obstinate unreceptive skepti- 
cism leads only to stagnation and death, and has 
certainly no place in an atmosphere where men are 
striving to unravel difficult and elusive prob- 
lems." (24) 

The successful therapist owes his position to a 
thorough attention to detail, no less than to his ap- 
preciation of probabilities, both diagnostic and 



248 THE INTERNAL SECRETIONS 

therapeutic; and if the possibiHties of hormone 
therapy materiahze, as they bid fair to do, there is 
every hope that the prevention and cure of the 
great white plague eventually may become an ac- 
complished fact. 



Some years have elapsed since the foregoing 
pages v^ere written. On reading them over I am 
reminded of some comment which I heard in Lon- 
don some months after this paper first appeared in 
print: Organotherapy is no more efficacious in 
the cure of tuberculosis than any other of the hun- 
dred and one therapeutic offerings. 

Of course this has more truth in it than fiction 
and it may be well to state unequivocally that none 
of the measures outlined are ''cures'' — the chapter 
heading calls them "adjuncts." 

However, of one thing I am convinced and that 
is that pancreatin is indeed a valuable remedy in 
tuberculosis, and that it acts in two separate and 
distinct ways. Besides its beneficent effects upon 
digestion, pancreatin seems to antagonize excessive 
adrenal activity, and it is now believed by several 
prominent investigators that the toxemia of tuber- 
culosis irritates the adrenals quite considerably and 
this hyperadrenia is responsible for several of the 
sympathetic symptoms such as dryness of the 
mouth, irritable heart, digestive crises and some of 
the sympathetic nervous derangement not uncom- 
mon in the tuberculous. 



IN PRACTICAL MEDICINE 249 

Whether or no we use organotherapy in treating 
tuberculosis, we must at least realize more than we 
have done that the tuberculous patient has an endo- 
crine system which is very likely to be affected, 
early in the course of the disease, and that if this 
is true, and how can it but be, the endocrine phase 
of tuberculosis is worth studying in the light of our 
present knowledge of the importance and all-em- 
bracing effects of the endocrine principles in health 
and disease. 

REFERENCES 

1. See American Medicine, New York, 1913, xix, 1, 5. 

2. Brunet, F. : 'Xe Sue Pulmonaire : Effets Physio- 
log-iques et Therapeutiques," Bull. Med., Paris, 1896, x, 
1239; ibid., C. R. Soc. Biol., Paris, 1897, 10, iv, 24. 

3. Grande, E. : "II Polmone un Opoterapia," Rif orma 
Med., Naples, 1897, xiii, 391. 

4. Lorand, A.: "Old Age Deferred," 1911, chap, 
xxxvii, p. 313. 

5. Schafer, E. A,: "The Nature, Origin, and Main- 
tenance of Life," Lancet, London, 1912, ii, 675. 

6. LerebouUet, P. : "Les Opotherapies dans la Tu- 
berculose," Paris Medical, 1912, 51, 586. 

7. Harrower, H. R. : "Therapeutic Action of Splenic 
Extract in Tuberculosis," Lancet, London, 1913, i, 524. 

8. Bayle, C. : "L'Opotherapie Splenique," Trans. Int. 
Tuber. Congr., Rome, 1912. 

9. Bayle, C. : "Splenic Opotherapy in Tuberculosis," 
Prescriber, Edinburgh, 1913, vii, 106. 

10. Schroder, G. : "Uber die Rolle der Milz als 
Schutzorgan gegen Tuberkulose Infektion" (I. Teil), Beitr. 
z. Kl. d. Tuberkulose, Wurzburg, 1909, xii, 323. 

11. Schroder, Kaufmann, and Kogel : Ibid. (II. Teil), 
Beitr. z. Kl. d. Tuberkulose, Wurzburg, 1912, xxiii, 1. 

12. Van Stockum, W. J. : "Die Therapeutische Wirk- 



250 THE INTERNAL SECRETIONS 

ung der mit Rontgen-Strahlen Vorbehandelten Milz bei 
Tuberkulose," Wien. Kl. Wochenschr., 1912, xxv, 1857. 

13. Editorial: "The Therapeutic Action of Splenic 
Extract," Univ. Med. Record, London, 1913, iii, 326. 

14. For further information, see "Opotherapie," P. 
Carnot, 1910, p. 479; "La Pratique de I'Opotherapie," L. 
Hallion, 1911, p. 22; "Les Produits Biologiques Medicin- 
aux," Byla and Delaunay, 1912, p. 302. 

15. Gerard, E., and Lemoine, G. : "Sur la Composi- 
tion de I'Extrait Ethere (Lipoide) de la Bile," Bull, et 
Mem. Soc. Med. d'Hop. de Paris, 1909, 3, xxviii, 935. See 
also Nord Med., Lille, 1909, xvi, 121, 241, 253; ibid., 1910, 
xvii, 129; Rev. Mod. de Med. et de Chir., Paris, 1910, viii, 
165 ; Med. Moderne, Paris, 1910, xxxi, 93. 

16. Gilbert, A., and Carnot, P.: "Note Preliminaire 
sur rOpotherapie Hepatique," C. R. Soc. Biol., Paris 1896, 
10, iii, 934; ibid., "De I'Opotherapie Hepatique dans les 
Hemorragies," C. R. Soc. Biol., Paris, 1897, 10, iv, 445. 

17. Carnot, P. : "L'Hemostase par Opotherapie He- 
patique," Paris Medical, 1911-12, 484. 

18. Parmentier, H. : "Traitement de la Tuberculosa 
Pulmonaire par les Extraits Hepatiques Totaux," Bull. Gen. 
de Ther., Paris, 1911, clxi, 218. 

19. Williams, Leonard: "The Therapeutic Promise 
of the Internal Secretions," Practitioner, London, 1911, 
Ixxxviii, 605. 

20. Brieger, L. : "Kombinationstherapie bei Pernizi- 
oser Anamie," Deut. Med. Wochenschr., Berlin, 1912, 
xxxviii, ii, 2154. 

21. Strubell, A.: "Der Einfluss der Hormone auf den 
Opsonischen Index," Berl. Kl. Wochenschr., 1912, xlix, 2350. 

22. Editorial : "New Aspects of Pancreatic Organo- 
therapy," Medical Record, New York, 1913, Ixxiii, 205. 

23. Boardman Reed: "Organic Derivatives in Indi- 
gestion," Amer. Jour. Gastro-Enterol., October, 1912 (abs. 
in Prescriber, Edinburgh, 1913, vii, 147). 

24. Williams, L. : "The Quickening Spirit," Brit. Med. 
Journ., 1910, ii, 928. 



INDEX 



Acidosis in Rickets 223 

Adenoids 152, 218 

Adrenal Asthenia 95 

— Cortex in Cancer 182 

— - Depletion — 14 

— Stigmata in Children 158 

Adrenals in Epilepsy 23 

— in General Practice 76 

— Relation to Neurasthenia 67 
Adrenalin, Oral Adminis- 
tration 229 

— Analgesic Effects 230 

— in Children's Diseases.— 234 

— in Nephritis 235 

— in Oto-Rhinology 217 

— in Spotted Fever 234 

— in War Medicine 68 

— Instillation Test 193 

Adrenin 78 

Alkalies in Hyperthyroid- 
ism - 188 

Alkalinity of Blood 37 

Altruistic Cell Activities 

46, 167 

Amenorrhea 107 

— Pituitary in 170 

Analgesic Effects of Ad- 
renalin 230 

Anoci-association 14, 63, 77 

Anterior Pituitary in Hy- 
perthyroidism 195 

Principle 156 

Asthenia 91 

— Adrenal 78 

— Endocrine 26, 91 

— Thyroid 94 

Asthenopia 219 

Blazek Twins 202 

Blindness, Pituitary Origin 59 

Cancer — Chemical Cause.... 20 

— Fundamentals of Causa- 

tion 172 

— Grafts, Effects of Castra- 

tion on 175 

— Organotherapy in. ...57, 163 



— Uterine, Mammary Ther- 

apy 171 

Calcium Lactate with Para- 
thyroid 23 

— Lactophosphate 222 

Cannon's findings 79 

Cellular Infiltration 144 

Cerehral Edema 23 

Children, Deiective from 

Endocrine Standpoint 148 

— Thyroid Dosage in 35,41 

— Thyroid Stigmata in 34 

Chromaffin Hormone ....78, 233 
Chronic Disease, Internal 

Secretions in 6 

Organotherapy in 163 

Cod Liver Oil 244 

in Rickets 225 

Constipation, Thyroid Ori- 
gin of 141 

Constitution, Jerry Built.... 36 
Corpus Luteum (Lutein) in 

Neurasthenia 108 

in Gynecology ....111, 120 

in Obesity 40 

■ with Thyroid 40,107 

Cretinism 149 

Deafness 213 

Defective Children 148 

Organotherapy 56 

Demineralization 180 

Dermographia 158 

— in Neurasthenia 65 

Diabetes Mellitus 25 

Diagnostic Use of Thyroid 

Extract 145 

Didymin 121 

Diet in Hyperthyroidism. ...191 

in Rickets 226 

Dizziness 213 

Dyscrinism 62, 67 

— Adrenal Origin 81 

— in Children 149 

— in Sex Disabilities 118 

Dysgenitalism 119 

(251) 



252 



THE INTERNAL SECRETIONS 



Dysmenorrhea, Adrenal Or- 
igin of 87 

— at Menopause 109 

— Pituitary in 170 

Therapy 107 

— Thyroid Origin of 34 

Dysovarism 86 

Dyspituitarism in Women..l09 
Dystrophia-adiposo geni- 
talis 96, 116 

Edema of Brain 137 

— Thyroid 144 

Ehrmann's Test 80 

Emotions, Influence on Ad- 
renals 76 

— Cause of Hyperthyroid- 

ism 81, 190 

Endocrine Stimulation 50 

— Disease, Syphilis a Fac- 

tor in 12, 27, 47, 49 

Endocrinasthenia 2 6, 91 

Epilepsy 22 

— Adrenal Factor in 83 

— Pancreatin in 84 

— Thyroid Gland in 136 

"Epinephrine" 235 

Eye Findings in Pituitary 

Disorder 220 

in Thyroid Disorder-219 

Fibroids 204, 207 

Focal Infection, Effect on 
Thyroid 190 

Froehlich's Syndrome 96 

Functional Disorders, Rela- 
tion of Endocrine Glands 16 

Gonad Extracts 120 

— Insufficiency 98,116 

Green Bone 223 

Hallion's Law 3, 50 

Heart Disease, Adrenal Ex- 
tract in 236 

— Failure, Treatment of-.-232 
Hemianopsia, Bitemporal. ...2 19 
Hepatic Extract in Hemop- 
tysis 244 

Hereditary Thyroid Insta- 
bility 141 

Homostimulation 3 



Hormone Balance ....20, 46, 240 

Hormone Therapy 255 

Hormotone 53, 71, 99, 110, 122 
Hyperadrenia 84 

— in Tuberculosis 248 

— Symptoms of 248 

Hyperovarism 204 

Hyperthyroidism 185 

— Diet in 191 

— Emotional Origin ....81,190 
Hypoadrenia 14 

— Acute 86 

— Influence on Gonads 117 

— in Neurasthenia 88 

— Symptoms of 63 

— Terminal 85 

Hypocrinism 105 

— See Pluriglandular In- 

sufficiency. 

— in Tuberculosis 239 

Hypopituitarism 96 

— Gonads in 116 

Hypothyroidism 106 

— See Thyroid Insufficiency. 

— in Cancer 176 

— in Rheumatism 129 

— Symptoms 33 

Hypoplasia 150 

Idiopathic Epilepsy 136 

Impotence 117, 120 

Indigestion of Adrenal Ori- 
gin 38 

Infantilism 150 

— Pituitary 96, 157 

Infiltration, Thyroid 144 

Intestinal Antisepsis 187 

— Irritation (Thyroid) ....189 

— Stasis 137 

Kephalin 217 

lioewi's Test 193 

Lymphatic Gland Extract..217 
Lymphocytosis 154 

Malaria, Adrenal Factor in 85 
Mamma an Internal Secre- 
tory Gland 196 

— Hormone 198 

Mammary Evolution 200 

— Extract 204 



IN PRACTICAL MEDICINE 



253 



Dosage of 211 

in Menorrhagia-105, 206 

in Uterine Cancer 171 

Menopausal Neurasthenia-108 
Menorrhagia, Mammary 

Therapy in 105, 206 

Menstrual Neurasthenia 104 

Metabolism, Thyroid Influ- 
ence on 132 

Mucous Colitis 187 

Myasthenia Gravis 98 

Nasal Disorders, Endocrine 
Glands in 212 

— Obstruction 139 

Nephritis, Adrenalin in 235 

Neurasthenia 24, 53 

— Adrenal Symptoms in 66, 87 

— and Shell Shock 62 

— in Women 100 

— Pituitary Origin 97 

Nocturnal Enuresis 33, 152 

Nutrition, Effects of Thy- 
roid on 34 

Obesity 40, 109 

Optic Atrophy, Primary 220 

Organotherapy, Forms of-.. 3 
Oto-Rhinology, Internal Se- 
cretions in 212 

Ovarian Neurasthenia 104 

— Rheumatism 132 

Ovaries, Influence on Mam- 
mae 201 

Pain Effects on Adrenals.... 14 

Palate, High Arched 153 

Pancreas, in Diabetes 25 

— Extract in Cancer 182 

Pancreatin in Epilepsy 84 

— in Hyperthyroidism 193 

— in Tuberculosis 245,248 

Paralysis Agitans, Impo- 
tence in 118 

Parathyroid Disease, Gon- 
ads in 118 

Parathyroids in Epilepsy.... 23 

Pedology 158 

Pineal, Influence upon Sex 
Development 118 

— Origin of Asthenia 98 



Pituitary and Thyroid Ther- 
apy 58 

: — Asthenia 96 

— Disease, Eye Findings.. ..219 
Successful Treatment 58 

— Extract in Epilepsy 23 

in Hyperthyroidism..l86 

in Impotence 120 

in Shock, etc 69 

— Infantilism 157 

— Relation to Growth 156 

Pituitrin, Heart Value of.... 9 

— to Forestall Bleeding....217 
Pluriglandular Insuffi- 
ciency 11, 43, 168 

— Therapy ..52, 58, 70, 74, 224 
Prophylaxis of Develop- 
mental Disorders 159 

Protan in Thyroid Diar- 
rhea 189 

Psychic Causes of Shock.... 64 
Pyorrhea in Hyperthyroid- 
ism 189 

— Relation to Goiter 216 

Raynaud's Disease 140 

Rheumatism ....18, 21, 123, 131 
Rickets 35, 155, 222 

— Cod Liver Oil in 225 

— Thymus Atrophy in 224 

Roberts-Hawley Lymph 

75, 99, 121 

Scaphoid Scapula 152 

Secretin 246 

— in Cancer 177 

Sellar Radiography 156 

Senility, Organotherapy in.. 55 

— Relation of Cancer 183 

Sequarine 121 

Sex Glands, see Gonads. 

— Disabilities 114 

Sexual Neurasthenia 107 

Shell Shock 62 

Sodium Bicarbonate ..188, 223 

— Cacodylate with Thyroid 39 

— Citrate in Rickets 223 

"Soldier's Heart" 66 

Spleen Extract 181, 242 

Spotted Fever, Adrenalin in 234 

Stasis, Intestinal 137 

Status Thymo-lymphaticus..l54 



254 



THE INTERNAL SECRETIONS 



Sugar Feeding in Cancer.— 182 

Sympathetico-tonus 78 

Suprarenals, see Adrenals. 
Syphilis 27 

— and Endocrine Disorder 12 

— in Pluriglandular Dis- 

ease 47, 49 

Tabloid Mixed Glands 

99, 122, 159 

Testicles, Influence on Can- 
cer Grafts 175 

Testicular Therapy 120 

Tethelin 156 

Thromboplastin 21 7 

Thymus Absence 155 

— Asthenia 97 

— Atrophy in Rickets 224 

— Enlargement 153 

— Extract 181 

— Relation to Rheumatism 134 

— Influence on Gonads IIS 

Thyroid Active Principle.... 10 

— Amenorrhea 107 

— Asthenia 94 

— Disorders, Minor 11 

Symptoms 38 

— Extract, Diagnostic Val- 

ue of 145 



Thyroid Extract, Dosage 

of 10, 32, 35, 40 

in Epilepsy 143 

in Rickets 224 

— Heart 66 

— Influence on Gonads. 115 

— Insufficiency, Minor ..11,30 

— in Rheumatism..22, 127,131 

— Preparations, Variations 

of 41 

— Stigmata in Children 34 

Tonsils, Relation to Goiter 215 

— Disease in Children 152 

Transmission of Endocrine 

Disorders 160 

Tuberculosis 18, 25 

— Organotherapy in 237 

— Pancreatin in 245 

Uterine Hemorrhage 

170, 171, 204 

Uterus, Cancer of 171 

— Functional Disorders .... 

87, 104, 107,109,170, 206 

Vegetable Consomme..l92, 227 
Virilism 117 

Weight, Loss of 65 



By the Same Author 

Practical Hormone Therapy 

A Manual of Organotherapy for General Practitioners 

Foreword by Prof. Dr. Artur Biedl 
A N intensely interesting book on the therapeutics of the 
'^*' internal secretory glands, which covers every phase 
of the subject in a clear and interesting manner. It is not 
a book on the internal secretory glands, but on the thera- 
peutics which the increasing knowledge of these organs 
has made possible. It contains : 

An extensive index — 26 columns, 37 chapters and 508 pages. 
A helpful glossary including 94 terms. 
An organotherapy dose-table with 165 indications. 
A useful list of 32 books on the internal secretions. 
An interesting chart of the relations of the ductless glands. 

Medical Record ( New York ) : Southern Medical Journal 

"In this, the latest contribu- (Mobile): "For the past few 
tion to the subject of the inter- 
nal secretions and of their val- 
ue as medicinal agents, the au- 
thor displays a comprehensive 
knowledge of the extensive lit- 
erature on this subject. In- 
deed, with the reference in the 
text and the bibliographic list 
at the end of each chapter 
there is presented a digest of 
almost everything that has 
been written on this subject. 

New York Medical Journal: 

"Harrower's book is very 
satisfactory and shows evidence 
of considerable research in the 
literature of the many subjects 
treated." 

The Medical Press (Dublin) : 
"The author has given us an 
extensive treatise on organo- 
therapy. He tells all that is 
known. . . . works of this 
kind which synoptize the re- 
sults obtained by countless sci- 
entific laborers are of much 
service." 

Price $4.50, prepaid $4.70. 

Obtainable from the Publisher of this book or from the 

Author direct — on approval if desired. 



years there has been almost un- 
paralleled progress in this 
branch of medicine. This book 
is particularly interesting in 
that it is the only one of its 
kind in English; it opens out 
before us the many possibili- 
ties of organotherapy and in- 
spires interest in the various 
and necessary metabolic chang- 
es wrought by the hormones." 

Buffalo Medical Journal: 
"We feel it is not too much to 
assert that this book marks an 
epoch in medical history. It 
systematizes and collates all 
the fundamental details and to 
a considerable degree affords 
work for future investigation." 

Boston Medical and Surgical 
Journal: "This work places in 
the hands of English readers a 
valuable compendium on a sub- 
ject hitherto treated almost 
solely by continental European 
writers." 



ENDOCRINOLOGY: 



The Bulletin of the Association for the Study of the 
Internal Secretions 

This new journal was originated by Doctor Harrower, 
and he is at this writing its Managing Editor. 

It is published quarterly and the first issue was pub- 
lished in 1917. 

It contains : 

Editorial articles by well-known authorities. 

Original communications, each accompanied by the comment 
of several, thus broadening their value to the reader. 

A review department containing numerous abstracts of cur- 
rent literature on the internal secretions, conveniently divided 
into four sections — General, Experimental, Clinical and Thera- 
peutic. 

A cross-index of subjects and authors in each journal. This 
is a decidedly valuable innovation in medical journalism, thus 
favoring the utmost convenience in looking up current literature. 

ENDOCRINOLOGY is an up-to-date resume of the 
subject and is but a part of the advantages of member- 
ship in this Association. The Secretary, Dr. Emil Goetsch, 
Johns Hopkins Hospital, Baltimore, Maryland, will be 
pleased to send further information to interested physicians 
on request. 



